Associations Between Commercial App Use and Physical Activity: Cross-Sectional Study.
In today's society, commercial physical activity apps (eg, Fitbit and Strava) are ubiquitous and hold considerable potential to increase physical activity behavior. Many commercial physical activity apps incorporate social components, in particular app-specific communities (allowing users to interact with other app users) or the capacity to connect to existing social networking platforms (eg, Facebook or Instagram). There is a growing need to gain greater insights into whether commercial physical activity apps and specific components of these apps (social components) are beneficial in facilitating physical activity. This study aimed to examine the relationship between the use of commercial physical activity apps and engagement in physical activity. The social components of commercial physical activity apps (app-specific communities and existing social networking platforms) were also explored. This involved isolating specific features (eg, sharing, providing, and receiving encouragement, comparisons, and competitions) of app-specific communities and existing social networking platforms that were most valuable in facilitating physical activity. A cross-sectional web-based survey was conducted. Participants were 1432 adults (mean age 34.1 years, 1256/1432, 88.00% female) who completed measures assessing physical activity, the use of commercial physical activity apps, and engagement with app-specific communities and existing social networking platforms. Overall, 53.14% (761/1432) of the sample reported engaging with a commercial physical activity app. The most commonly used apps were Fitbit (171/761, 22.5%), Strava (130/761, 17.1%), and Garmin (102/761, 13.4%). The use of physical activity apps was significantly associated with physical activity. Notably, the use of app-specific communities and existing social networking platforms facilitated significantly greater engagement in physical activity. The features of app-specific communities that were most beneficial in promoting engagement in physical activity were providing encouragement to a partner, receiving encouragement from close friends and family, and engaging in competitions with members of public app-specific communities. In relation to existing social networking platforms, sharing physical activity posts predicted engagement in physical activity. The findings indicate that app-specific communities and existing social networking platforms are components of apps that are fundamental in facilitating physical activity. They further suggest that commercial physical activity apps afford high population level reach and hold great potential to promote engagement in physical activity, an important public health consideration.


Now you C me: a case of scurvy presenting as depression and anaemia.
A 66-year-old Caucasian woman was admitted with deteriorating mental health in the setting of background history of schizophrenia and depression. Her husband reported that she had increasing negative thoughts and decreased motivation regarding her self-care over a few weeks with no obvious stressors. Initial laboratory tests were unremarkable except for isolated normocytic anaemia. Physical examination revealed widespread bilateral upper limb ecchymoses and lower limb petechial rash. After an extensive investigation with no definitive results to explain her clinical presentations, diagnosis of scurvy was suspected and confirmed with severely low serum vitamin C level. Her clinical symptoms improved markedly with oral supplementation, which further supported the diagnosis of scurvy. Although it is now a rare condition in developed countries, this case will remind modern medical practitioners that patients with scurvy may present with non-specific symptoms and clinical findings such as depression and anaemia.


Preference for Object Relative Clauses in Chinese Sentence Comprehension: Evidence From Online Self-Paced Reading Time.
Most prior studies have reported that subject-extracted relative clauses (SRCs) are easier to process than object-extracted relative clauses (ORCs). However, whether such an SRC preference is universal across different languages remains an open question. Several reports from Chinese have provided conflicting results; thus, in the present study, we conducted two self-paced reading experiments to examine the comprehension of Chinese relative clauses. The results demonstrated a clear ORC preference that Chinese ORCs were easier to comprehend than Chinese SRCs. These findings were most compatible with the prediction of the integration cost account, which claims that the processing difference between SRCs and ORCs arises at the point of dependency formation. The ORC preference in Chinese poses a challenge to the universality of the SRC preference assumed by the structural distance hypothesis and highlights the values of cross-linguistic research.


The vaccinia virus A4OR gene product is a nonstructural, type II membrane glycoprotein that is expressed at the cell surface.
Gene A40R from vaccinia virus (VV) strain Western Reserve has been characterized. The open reading frame (ORF) was predicted to encode a 159 amino acid, 18152 Da protein with amino acid similarity to C-type animal lectins and to the VV A34R protein, a component of extracellular enveloped virus (EEV). Northern blotting and S1 nuclease mapping showed that gene A40R is transcribed early during infection from a position 12 nucleotides upstream of the ORF, producing a transcript of approximately 600 nucleotides. Rabbit anti-sera were raised against bacterial fusion proteins containing parts of the A40R protein. These were used to identify an 18 kDa primary translation product and N- and O-glycosylated forms of 28, 35 and 38 kDa. The A40R proteins were detected early during infection, formed higher molecular mass complexes under non-reducing conditions and were present on the cell surface but absent from virions. The proteins partitioned with integral membrane proteins in Triton X-114. Canine pancreatic microsomal membranes protected in vitro-translated A40R from proteinase K digestion, suggesting the A40R protein has type II membrane topology. A mutant virus with the A40R gene disrupted after amino acid 50, so as to remove the entire lectin-like domain, and a revertant virus were constructed. Disruption of the A40R gene did not affect virus plaque size, in vitro growth rate and titre, EEV formation, or virus virulence in a murine intranasal model.


Human solid tumors contain high endothelial venules: association with T- and B-lymphocyte infiltration and favorable prognosis in breast cancer.
The mechanisms governing infiltration of lymphocytes into tumors remain poorly characterized, in spite of the critical impact of these cells on patient prognosis and therapeutic responses. High endothelial venules (HEV) are blood vessels found in lymphoid tissues, specialized in lymphocyte recruitment, but their implications in human cancer are unknown. In this article, we report the presence of MECA 79(+) blood vessels displaying all the phenotypic characteristics of HEVs in most of the 319 human primary solid tumors, including melanomas, breast, ovarian, colon, and lung carcinomas, analyzed. Tumor HEVs were specifically located within lymphocyte-rich areas, and their density within the tumor stroma was a strong predictor of infiltration by CD3(+) and CD8(+) T cells as well as B cells. Large-scale flow cytometric and quantitative reverse transcriptase-PCR analyses in freshly operated breast tumors revealed that high densities of tumor HEVs correlated with increased naive, central memory and activated effector memory T-cell infiltration and upregulation of genes related to T-helper 1 adaptive immunity and T-cell cytotoxicity. Finally, in a retrospective cohort of 146 invasive breast cancer patients, we found that high densities of tumor HEVs independently conferred a lower risk of relapse and significantly correlated with longer metastasis-free, disease-free, and overall survival rates. Together, our findings suggest that tumor HEVs function as major gateways for lymphocyte infiltration into human tumors, and may represent attractive targets for cancer diagnosis and therapy.


Revisited measles and chickenpox dynamics through orthogonal transformation.
The question addressed is whether or not childhood epidemics such as measles and chickenpox are characterized by low-dimensional chaos. We propose a new method for the detection and extraction of hidden periodic components embedded in an irregular cyclical series, and study the characterization of the epidemiological series in terms of the characteristic features or periodicity attributes of the extracted components. It is shown that the measles series possesses two periodic components each having a period of one year. Both the periodic components have time-varying pattern, and the process is nonlinear and deterministic; there is no evidence of strong chaoticity in the measles dynamics. The chickenpox series has one seasonal component with stable pattern, and the process is deterministic but linear, and hence non-chaotic. We also propose surrogate generators based on null hypotheses relating to the variability of the periodicity attributes to analyse the dynamics in the epidemic series. The process dynamics is also studied using seasonally forced SEIR epidemic model, and the characterization performance of the proposed schemes is assessed.


Clinical significance of frizzled homolog 3 protein in colorectal cancer patients.
Frizzled homolog 3 receptor was up-regulated in several gastrointestinal cancers such as esophageal and gastric cancers. Moreover, frizzled homolog 3 has recently reported to be expressed in colorectal adenoma specimens. In the present study, we investigated the clinical significance of frizzled homolog 3 protein in colorectal cancer patients. Using immunocytochemical staining, frizzled homolog 3 expression was examined in 186 colorectal cancer specimens, 79 colorectal adenoma specimens, 133 colorectal polyp specimens, 127 colorectal cancer specimens with lymph node and/or distant metastasis, 310 specimens of various non-colorectal cancer metastatic carcinomas and 40 specimens with simultaneous occurrence of colorectal cancer, colorectal adenoma and colorectal polyp. Statistical analysis was used to correlate frizzled homolog 3 protein expression to the clinicohistopathological factors, recurrence/metastasis and survival after follow-up for 42 months in colorectal cancer patients. Frizzled homolog 3 protein was expressed in 100% colorectal cancer specimens, 89% colorectal adenoma specimens, 75% colorectal polyp specimens and 69% normal colorectal epithelial tissues. Moreover, frizzled homolog 3 immunocytochemical scores were highly correlated with colorectal cancer progression. Furthermore, frizzled homolog 3 was expressed in a comparatively lower percentage of metastatic hepatocellular carcinoma and metastatic renal clear cell carcinoma with focal and very weak staining than other metastatic tumor types. On the other hand, the frizzled homolog 3 immunocytochemical scores of colorectal adenomas with synchronous colorectal carcinomas were significantly higher than those of pure colorectal adenomas. Statistical analysis showed that frizzled homolog 3 immunocytochemical scores were associated with Dukes stage and lymph node status. Finally, stratified groups of colorectal cancer patients had significant differences in their recurrence/metastasis and survival. In conclusion, the present large-scale study has clearly showed that frizzled homolog 3 protein can generate clinically important information for colorectal cancer patients.


Human kidney thiopurine methyltransferase. Purification and biochemical properties.
Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurines and thiopyrimidines. Human kidney TPMT was purified over 300-fold and its biochemical properties were determined. TPMT was "soluble" and had a molecular weight of approximately 36,000 daltons as estimated by gel filtration chromatography. The pH optimum of the purified TPMT was 6.7. "True" Km values for 6-mercaptopurine (6-MP) and S-adenosyl-L-methionine (SAM), the two cosubstrates for the reaction, were 0.30 mM and 2.7 microM respectively. "Apparent" Km values for 6-thioguanine and 2-thiouracil, two other methyl acceptor substrates, were 0.55 and 2.0 mM respectively. Aliphatic thiol compounds were either poor substrates for TPMT or were not methylated. S-Adenosyl-L-homocysteine was a competitive inhibitor of TPMT when the varied substrate was SAM, and 6-methylmercaptopurine was a noncompetitive inhibitor with respect to 6-MP. Purified TPMT was neither activated nor inhibited by 1 mM Ca2+ or Mg2+, but exposure to reagents such as N-ethylmaleimide and ethacrynic acid that interact with sulfhydryl groups inactivated the enzyme. Tropolone inhibited TPMT with a Ki of approximately 0.85 mM. Finally, human kidney TPMT activity could be distinguished from human kidney thiol methyltransferase (EC 18.104.22.168) activity on the basis of subcellular distribution, substrate specificity, kinetic characteristics and differential sensitivity to inhibitors.


Psoriasis in Children and Adolescents: Diagnosis, Management and Comorbidities.
Psoriasis is a common chronic immune-mediated inflammatory skin disorder and begins in childhood in almost one-third of the cases. Although children present with the same clinical subtypes of psoriasis seen in adults, lesions may differ in distribution and morphology, and their clinical symptoms at presentation may vary from those reported by adult patients. Nevertheless, diagnosis of psoriasis is primarily based on clinical features. Pediatric psoriasis can have a profound long-term impact on the psychological health of affected children. Additionally, pediatric psoriasis has been associated with certain comorbidities, such as obesity, hypertension, hyperlipidemia, diabetes mellitus and rheumatoid arthritis, making early diagnosis and management essential. As guidelines are lacking and most (systemic) treatments are not approved for use in children, treatment of pediatric psoriasis remains a challenge. A prospective, multicenter, international registry is needed to evaluate these treatments in a standardized manner and ultimately to develop international guidelines on pediatric psoriasis. This article reviews current concepts in pediatric psoriasis including epidemiology, clinical features, diagnosis, the role of topical and systemic agents and the association with other morbidities in childhood.


Human papilloma virus vaccines: A comprehensive narrative review.
Cervical cancer is one of the most common cancers in women aged 15-44 years in the world, with more than three-quarters of cases diagnosed at a locally advanced clinical stage with minor prospects of survival. Although only a small percentage of women with Human Papilloma Virus (HPV) develop cervical cancer and most of the HPV infections are cleared subsequently at primary stage itself, but seroconversion not always guarantees that the individual is immune to HPV. The advent of the cervical carcinoma vaccine has raised the expectations that eradication of cervical carcinoma might be possible in the near future as it exhibited remarkably high efficacy against the vaccine-specific types in naive women with no serious vaccine-related adverse events. Few prophylactic HPV vaccines are currently licensed in over 100 countries. It has also been suggested that vaccinating both men and women is more beneficial than vaccinating only females. Vaccination is a cost-effective strategy to reduce the incidence of cervical cancer and mortality compared to no vaccination based on the cost of cancer treatment. Well-coordinated vaccination strategy with focus on adolescent girls and if possible, boys can lead to dramatic impact on disease reduction around the world.


[Multisite-based approach to assure inter-assay system compatibility among different exclusive-typed immunoassay systems through determining exchanged calibrators].
It is well known that most exclusive-typed immunoassay systems are highly precise but are poor in compatibility of their determinations. Thus, it is difficult to compare the determinations among different systems, posing problems when a patient is transferred to different hospitals or when a laboratory intends to change the system currently used. In the study, we tried to approach how to assure inter-immunoassay compatibility among four different systems through determination of the exchanged calibrators. First, determinations of total protein and albumin, and electrophoretic fractionation demonstrated marked differences among calibrators in their protein constituent. Some calibrators were prepared with human sera, but others were with inorganic or non-human albumin-based solution. Regression analysis of calibrators between the indicated concentrations by manufacturers and those actually determined by the different immunoassay systems revealed that; most slopes were closed to 1.0 for alpha-fetoprotein and prostate-specific antigen, but widely dissociated from 0.28 to 4.71 for CA19-9. In evaluation of clinical serum samples, determinations by one immunoassay system were compared with those converted based on a linear regression equation that was obtained by determination of the exchanged calibrators. However, this procedure could not improve compatibility, and positive effects of conversion varied by immunoassay systems combined, and also by test parameters. With these, we concluded that simple conversion of determinations by using the exchanged calibrators and a statistical linear regression could not provide us with the expected compatibility. Thus, standardization of target molecules or probes, and of calibrator constituent were urgent issue to assure inter-immunoassay compatibility.


The minimally invasive interbody selection algorithm for spinal deformity.
Minimally invasive surgery (MIS) for spinal deformity uses interbody techniques for correction, indirect decompression, and arthrodesis. Selection criteria for choosing a particular interbody approach are lacking. The authors created the minimally invasive interbody selection algorithm (MIISA) to provide a framework for rational decision-making in MIS for deformity. A retrospective data set of circumferential MIS (cMIS) for adult spinal deformity (ASD) collected over a 5-year period was analyzed by level in the lumbar spine to identify surgeon preferences and evaluate segmental lordosis outcomes. These data were used to inform a Delphi session of minimally invasive deformity surgeons from which the algorithm was created. The algorithm leads to 1 of 4 interbody approaches: anterior lumbar interbody fusion (ALIF), anterior column release (ACR), lateral lumbar interbody fusion (LLIF), and transforaminal lumbar interbody fusion (TLIF). Preoperative and 2-year postoperative radiographic parameters and clinical outcomes were compared. Eleven surgeons completed 100 cMISs for ASD with 338 interbody devices, with a minimum 2-year follow-up. The type of interbody approach used at each level from L1 to S1 was recorded. The MIISA was then created with substantial agreement. The surgeons generally preferred LLIF for L1-2 (91.7%), L2-3 (85.2%), and L3-4 (80.7%). ACR was most commonly performed at L3-4 (8.4%) and L2-3 (6.2%). At L4-5, LLIF (69.5%), TLIF (15.9%), and ALIF (9.8%) were most commonly utilized. TLIF and ALIF were the most selected approaches at L5-S1 (61.4% and 38.6%, respectively). Segmental lordosis at each level varied based on the approach, with greater increases reported using ALIF, especially at L4-5 (9.2°) and L5-S1 (5.3°). A substantial increase in lordosis was achieved with ACR at L2-3 (10.9°) and L3-4 (10.4°). Lateral interbody arthrodesis without the use of an ACR did not generally result in significant lordosis restoration. There were statistically significant improvements in lumbar lordosis (LL), pelvic incidence-LL mismatch, coronal Cobb angle, and Oswestry Disability Index at the 2-year follow-up. The use of the MIISA provides consistent guidance for surgeons who plan to perform MIS for deformity. For L1-4, the surgeons preferred lateral approaches to TLIF and reserved ACR for patients who needed the greatest increase in segmental lordosis. For L4-5, the surgeons' order of preference was LLIF, TLIF, and ALIF, but TLIF failed to demonstrate any significant lordosis restoration. At L5-S1, the surgical team typically preferred an ALIF when segmental lordosis was desired and preferred a TLIF if preoperative segmental lordosis was adequate.


Assessment of linguistic abilities in Italian children with specific language impairment.
This study aims to describe in detail the linguistic skills of a large group of SLI participants. Particular attention is paid to the analysis of age-related effects on their linguistic performance and to whether a linguistic assessment of a narrative task can capture language impairments that might not be adequately pointed out by standardized neuropsychological tests assessing linguistic functions. The narratives produced by 62 children diagnosed with SLI with mixed expressive-receptive disorders were compared to those provided by a group of 195 children with Typical Language Development matched for chronological age and level of formal education. Furthermore, an age-related groups' performance analysis has been performed in order to determine possible correlations between patients' ages and types of language impairment. The SLI participants produced an amount of words comparable to that produced by the control group, albeit in a simpler fashion, as their narratives were teeming with omissions and/or substitutions of bound and free morphemes. These data suggest that the domains of morphosyntax and syntax were particularly impaired.


Introns control expression of sucrose transporter LeSUT1 in trichomes, companion cells and in guard cells.
In solanaceous plants such as tomato and tobacco, the sucrose transporter SUT1 is crucial for phloem loading. Using GUS as a reporter, the promoter and other regulatory cis elements required for the tomato LeSUT1 expression were analyzed by heterologous expression of translational chimeric constructs in tobacco. Although LeSUT1 is highly expressed at the RNA level, GUS expression under the control of a 1.8 kb LeSUT1 promoter resulted in few plants expressing GUS. In GUS-positive transformants, expression levels were low and limited to leaf phloem. Increasing or decreasing the length of LeSUT1 promoter did not lead to a significant increase in positive transformants or higher expression levels. Translational fusion of GUS to the LeSUT1 C-terminus in a construct containing all exons and introns and the 3'-UTR led to a higher number of positive transformants and many plants with high GUS activity. LeSUT1 expression was detected in ab- and adaxial phloem companion cells, trichomes and guard cells. The role of individual introns in LeSUT1 expression was further analyzed by placing each LeSUT1 intron into the 5'-UTR within the 2.3 kb LeSUT1 promoter construct. Results showed remarkable functions for the three introns for SUT1 expression in trichomes, guard cells and phloem cells. Intron 3 is responsible for expression in trichomes, whereas intron 2 is necessary for expression in companion cells and guard cells. The combination of all introns is required for the full expression pattern in phloem, guard cells and trichomes.


Hormonal control of postnatal development of corticosteroid-binding globulin.
The hormonal regulation of the ontogenic rise in serum corticosteroid-binding globulin (CBG) has been studied in the rat. Pups received daily injections of estrogens (either estradiol, estrone, or diethylstilbesterol, each at 0.05 microgram/g body wt) or thyroxine (0.1 microgram/g body wt) on postnatal days 2-7. When CBG binding capacity was determined on day 8, only the thyroxine-injected pups were found to have elevated CBG. This effect of thyroxine on CBG binding capacity was further studied by daily administration of the hormone (0.1 microgram.g body wt-1.day-1) between postnatal days 5-12. This caused a precocious rise in serum CBG, with CBG values 6- to 38-fold higher than euthyroid controls on days 8, 10, and 12. Conversely, in pups made hypothyroid by administration of propylthiouracil, the normal ontogenic increase in CBG was suppressed. Thyroxine replacement resulted in the reappearance of the CBG rise. These results suggest that the developmental rise in the binding capacity of CBG is independent of estradiol and estrone and instead is elicited by the rising concentrations of circulating thyroxine that normally occur in the early postnatal period.


Protein kinase STK25 aggravates the severity of non-alcoholic fatty pancreas disease in mice.
Characterising the molecular networks that negatively regulate pancreatic β-cell function is essential for understanding the underlying pathogenesis and developing new treatment strategies for type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic fat storage, meta-inflammation, and fibrosis in liver and skeletal muscle. Here, we assessed the role of STK25 in control of progression of non-alcoholic fatty pancreas disease in the context of chronic exposure to dietary lipids in mice. We found that overexpression of STK25 in high-fat-fed transgenic mice aggravated diet-induced lipid storage in the pancreas compared with that of wild-type controls, which was accompanied by exacerbated pancreatic inflammatory cell infiltration, stellate cell activation, fibrosis and apoptosis. Pancreas of Stk25 transgenic mice also displayed a marked decrease in islet β/α-cell ratio and alteration in the islet architecture with an increased presence of α-cells within the islet core, whereas islet size remained similar between genotypes. After a continued challenge with a high-fat diet, lower levels of fasting plasma insulin and C-peptide, and higher levels of plasma leptin, were detected in Stk25 transgenic vs wild-type mice. Furthermore, the glucose-stimulated insulin secretion was impaired in high-fat-fed Stk25 transgenic mice during glucose tolerance test, in spite of higher net change in blood glucose concentrations compared with wild-type controls, suggesting islet β-cell dysfunction. In summary, this study unravels a role for STK25 in determining the susceptibility to diet-induced non-alcoholic fatty pancreas disease in mice in connection to obesity. Our findings highlight STK25 as a potential drug target for metabolic disease.


Cortical and amygdalar neuronal ensembles in alcohol seeking, drinking and withdrawal.
Alcohol induces many alterations in the brain that are thought to contribute to alcohol addiction. Most of the known alterations are induced in all neurons of a brain area or all neurons of a given cell type, regardless of whether they were activated during behavior. While these alterations can have important modulatory effects on behavior, they cannot explain why animals respond specifically to alcohol-paired cues as opposed to all other non-paired cues and evoke highly specific goal-directed learned responses in models of drug craving. As an alternative, we hypothesize another class of alterations that are induced only within sparsely distributed patterns of neurons, called neuronal ensembles, that are selectively activated by alcohol-specific cues during behavior and encode the long-term memories underlying these learned behaviors in animal models of alcohol addiction. Here we review recent studies and techniques used to identify the role of neuronal ensembles in animal models of different phases of the alcohol addiction cycle. This article is part of the Special Issue entitled "Alcoholism".


Providing Feedback for Learners in Virtual Visits Using a Standardized Direct Observation Assessment Form.
This article was migrated. The article was marked as recommended. Background: The COVID-19 pandemic has created a rapid shift in primary care from in-clinic visits to virtual visits. Physicians must adapt to supervising learners in these virtual visits. Multiple factors should be considered prior to a virtual clinic day, including the type of virtual visit, the learner's level of competence, and the patient's characteristics and concerns. Although the approach to supervision of virtual visits may vary, direct supervision and assessment should still continue in a standardized and effective manner. Aim: We have created a novel virtual visit direct observation assessment form to facilitate feedback when physicians are supervising learners in virtual care. Methods: We gathered and reviewed information from the College of Family Physicians of Canada and other resources that were rapidly disseminated during the COVID-19 pandemic to create a direct observation assessment form based on evolving best practice. We conducted an internal peer-review process at our institution for the direct observation assessment form. We then distributed the form across our provincial academic sites for use. Results: The authors present a standardized virtual visit direct observation assessment form for use when supervising learners. This form assesses important skills for effective patient care in a virtual setting. The criteria consist of general competencies and corresponding detailed skills. Conclusion: As primary care incorporates more virtual visits, direct supervision and assessment of residents must remain a priority for academic medicine. The virtual supervision assessment form can be used as an assessment modality, a springboard for feedback, and a learning tool for residents and supervisors as they provide care in an increasingly virtual environment.


AB-QTL analysis in winter wheat: I. Synthetic hexaploid wheat (T. turgidum ssp. dicoccoides x T. tauschii) as a source of favourable alleles for milling and baking quality traits.
The advanced backcross QTL (AB-QTL) strategy was utilised to locate quantitative trait loci (QTLs) for baking quality traits in two BC(2)F(3) populations of winter wheat. The backcrosses are derived from two German winter wheat cultivars, Batis and Zentos, and two synthetic, hexaploid wheat accessions, Syn022 and Syn086. The synthetics originate from hybridisations of wild emmer (T. turgidum spp. dicoccoides) and T. tauschii, rather than from durum wheat and T. tauschii and thus allowed for the first time to test for exotic QTL effects on wheat genomes A and B in addition to genome D. The investigated quality traits comprised hectolitre weight, grain hardness, flour yield Type 550, falling number, grain protein content, sedimentation volume and baking volume. One hundred and forty-nine SSR markers were applied to genotype a total of 400 BC(2)F(3) lines. For QTL detection, a mixed-model ANOVA was conducted, including the effects DNA marker, BC(2)F(3) line, environment and marker x environment interaction. Overall 38 QTLs significant for a marker main effect were detected. The exotic allele improved trait performance at 14 QTLs (36.8%), while the elite genotype contributed the favourable effect at 24 QTLs (63.2%). The favourable exotic alleles were mainly associated with grain protein content, though the greatest improvement of trait performance due to the exotic alleles was achieved for the traits falling number and sedimentation volume. At the QTL on chromosome 4B the exotic allele increased the falling number by 19.6% and at the QTL on chromosome 6D the exotic allele led to an increase of the sedimentation volume by 21.7%. The results indicate that synthetic wheat derived from wild emmer x T. tauschii carries favourable QTL alleles for baking quality traits, which might be useful for breeding improved wheat varieties by marker-assisted selection.


Interlocked bivalents in reconstructed metaphase I cells of bread wheat.
Complete reconstructions of all the bivalents were made from electron micrographs of serial sections through six pollen mother cells at metaphase I of meiosis in Triticum aestivum (hexaploid bread wheat). At least two of these metaphases contained interlocked pairs of bivalents. In one, two ring bivalents were interlocked, while in another a rod bivalent ran through the centre of a ring bivalent. Two other groups of bivalents were too closely appressed to allow separation into individual bivalents and may have contained interlocks. Meiosis in other anthers of the same plants examined by light microscopy was considered normal. The frequency of interlocking found was much higher than reported from light-microscope spreads. Not all interlocks in metaphase I cells need adversely affect meiosis, but knowledge of their regularity and form may facilitate understanding the processes of chromosome pairing.


Who has second-trimester abortions in the United States?
Little is known about the characteristics of second-trimester abortion patients. Data come from a national sample of 9493 women obtaining abortions in 2008. Chi-square statistics and logistic regression were used to examine demographic characteristics of women having abortions at 13 or more weeks since last menstrual period (LMP) and women having abortions at 13-15 weeks LMP compared to 16+ weeks LMP. In 2008, 10.3% of abortions in the United States were 13 weeks LMP or later, including 4.0% at 16+ weeks. Groups most likely to have abortions at 13 weeks or later included black women, women with less education, those using health insurance to pay for the procedure and those who had experienced three or more disruptive events in the last year. Groups more likely to have an abortion at 16 weeks or later included black women, higher income women and those paying with health insurance. Black women and those with less education would most benefit from increased availability of first-trimester abortion services.


Intestinal enterokinase deficiency. Occurrence in two sibs and age dependency of clinical expression.
Intestinal enterokinase deficiency in 2 sibs in described. A boy failed to gain weight and had vomiting, diarrhoea, oedema, hypoproteinaemia, and anaemia in early infancy. His duodenal juice contained very low or absent proteolytic enzyme activity, which increased markedly after addition of enterokinase. He was treated with pancreatic extract and gained weight rapidly. At 44 months of age he is normal, apart from some development delay, and no longer needs pancreatic extract. His older sister, who had had similar symptoms in early infancy but then grew normally, had the same abnormality in her duodenal juice when seen at 4 years of age. Enterokinase activity was virtually absent in the duodenal mucosa of both patients. Mucosal morphology was normal. The findings suggest that enterokinase deficiency is an inherited congenital defect and not the result of mucosal damage. Affected patients may show spontaneous improvement and normal growth after the age of 6 to 12 months. This phenomenon may be related to the decreasing growth volocity during the first 2 years of life and the concimitant decrease in protein requirements per unit bodyweight.


Immunoregulatory roles of eosinophils: a new look at a familiar cell.
Eosinophils are usually considered as end-stage degranulating effector cells of innate immunity. However, accumulating evidence has revealed additional roles for eosinophils that are immunoregulatory in nature in both the adaptive and innate arms of immunity. Specifically, eosinophils have key immunoregulatory roles as professional antigen-presenting cells and as modulators of CD4(+) T cell, dendritic cell, B cell, mast cell, neutrophil, and basophil functions. This review addresses the emerging immunoregulatory roles of eosinophils with a focus on recent data that support this new paradigm. Recognizing both the effector and immunoregulatory functions of eosinophils will enable a fuller understanding of the roles of eosinophils in allergic airways inflammation and may be pertinent to therapies that target eosinophils both for their acute and ongoing immunomodulatory functions.


The uncoupled state of the human formyl peptide receptor.
The formyl peptide receptor (FPR) has been widely used to study the kinetics of the interaction between ligand, receptor and G protein with real-time fluorescence methods. Because the wild type receptor rapidly signals, and is then desensitized and internalized once occupied by ligand, it has been difficult to study the uncoupled receptor form. We have examined a mutant form of the FPR expressed in U937 cells that does not bind G protein and is thus ideal to study the uncoupled form of the FPR in the intact cell. Using kinetic flow cytometry, we have measured the dissociation kinetics of a fluorescent ligand from this mutant in intact, permeabilized and fixed cells. We observed a novel uncoupled receptor form in the intact cell with a dramatically reduced off-rate (approximately 0.02 s-1) from LR in a broken cell preparation (approximately 0.2 s-1). Both receptor forms are retained in the presence of formaldehyde. We also observed this novel receptor form coexisting with the LRG complex when the wild type receptor is fixed in neutrophils or transfectants. These results complex when the wild type receptor is fixed in neutrophils o transfectants. These results lead us to suggest that there are distinct receptor structures in cells and membranes and that only a fraction of receptors in intact cells exist in the uncoupled form.


Saccadic model of eye movements for free-viewing condition.
In this paper, we propose a new framework to predict visual scanpaths of observers while they freely watch a visual scene. The visual fixations are inferred from bottom-up saliency and several oculomotor biases. Bottom-up saliency is represented by a saliency map whereas the oculomotor biases (saccade amplitudes and saccade orientations) are modeled using public eye tracking datasets. Our experiments show that the simulated scanpaths exhibit similar trends of human eye movements in a free-viewing condition. The generated scanpaths are more similar to human scanpaths than those generated by two existing methods. In addition, we show that computing saliency maps from simulated visual scanpaths allows to outperform existing saliency models.


Vitamin D Deficiency, Supplementation, and Cardiovascular Health.
Vitamin D has been traditionally recognized as a vitamin quintessential for bone-mineral health. In the past 2 decades, numerous experimental and observational studies have highlighted the role of vitamin D in immunity, metabolic syndrome (obesity and diabetes), cancers, renal disease, memory, and neurological dysfunction. In this article, we review important studies that focused on the impact of vitamin D on blood pressure, myocardial infarction, peripheral arterial disease, heart failure, and statin intolerance. Amidst the current pool of ambiguous evidence, we intend to discuss the role of vitamin D in "high-value cardiovascular health care".


School Environments and Elementary School Children's Well-Being in Northwestern Mexico.
School environment refers to the set of relationships that occur among members of a school community that are determined by structural, personal, and functional factors of the educational institution, which provide distinctiveness to schools. The school environment is an important factor when evaluating student well-being. Previous findings have shown that variables such as physical, academic, and social dimensions influence school environments. This research seeks to explain the relationship between school environment and the well-being of primary education students. To carry out this research, a total of 405 students from four public elementary schools in northwestern Mexico were selected to participate. The instrument used to measure the variables and the relationship of school environment and well-being is based on the three dimensions of school environment proposed by Kutsyuruba et al. (2015): Physical, social, and academic. Statistical analyses were carried out to determine the reliability and validity of the measurement scales using SPSS V20 and EQS software. Confirmatory factor analysis models were tested to determine the construct validity of each scale; then, an analysis via structural equation modeling was made to form an explanatory model obtaining acceptable practical and statistical indicators. Among the relationships in this study, our research identified the variable of school environments as an outcome determined by physical, academic, and social factors. School environment and student well-being variables were also found to be correlated.


[Variability of blood pressure measured using an oscillometric method in children 4 to 48 months of age].
The usual method of measuring arterial blood pressure cannot be used in children less than 4 years of age because of lack of cooperation. We investigated variations of blood pressure measured during 20 minutes by an oscillometric method (Dinamap) in 100 children aged 4 to 48 months and tried to come up with some recommendations for measuring and interpreting blood pressure. Serial blood pressure recordings showed poor reproducibility due to movements which are impossible to avoid and which account for wide variations. Because of this variability, a single measurement is inadequate and must be repeated. The average of repeated recordings does not seem to be a reliable parameter. We suggest that the lower measured value (minima) as the only parameter allowing us to track the progressive increase in blood pressure with age. The data probably explain the large discrepancies between published studies taking into account the use of different methods.


The search for reliable biomarkers of disease in multiple chemical sensitivity and other environmental intolerances.
Whilst facing a worldwide fast increase of food and environmental allergies, the medical community is also confronted with another inhomogeneous group of environment-associated disabling conditions, including multiple chemical sensitivity (MCS), fibromyalgia, chronic fatigue syndrome, electric hypersensitivity, amalgam disease and others. These share the features of poly-symptomatic multi-organ cutaneous and systemic manifestations, with postulated inherited/acquired impaired metabolism of chemical/physical/nutritional xenobiotics, triggering adverse reactions at exposure levels far below toxicologically-relevant values, often in the absence of clear-cut allergologic and/or immunologic involvement. Due to the lack of proven pathogenic mechanisms generating measurable disease biomarkers, these environmental hypersensitivities are generally ignored by sanitary and social systems, as psychogenic or "medically unexplained symptoms". The uncontrolled application of diagnostic and treatment protocols not corresponding to acceptable levels of validation, safety, and clinical efficacy, to a steadily increasing number of patients demanding assistance, occurs in many countries in the absence of evidence-based guidelines. Here we revise available information supporting the organic nature of these clinical conditions. Following intense research on gene polymorphisms of phase I/II detoxification enzyme genes, so far statistically inconclusive, epigenetic and metabolic factors are under investigation, in particular free radical/antioxidant homeostasis disturbances. The finding of relevant alterations of catalase, glutathione-transferase and peroxidase detoxifying activities significantly correlating with clinical manifestations of MCS, has recently registered some progress towards the identification of reliable biomarkers of disease onset, progression, and treatment outcomes.


Fluorescent magnetic hybrid nanoprobe for multimodal bioimaging.
A fluorescent magnetic hybrid imaging nanoprobe (HINP) was fabricated by the conjugation of superparamagnetic Fe3O4 nanoparticles and visible light emitting (∼600 nm) fluorescent CdTe/CdS quantum dots (QDs). The assembly strategy used the covalent linking of the oxidized dextran shell of magnetic particles to the glutathione ligands of QDs. The synthesized HINP formed stable water-soluble colloidal dispersions. The structure and properties of the particles were characterized by transmission electron and atomic force microscopy, energy dispersive x-ray analysis and inductively coupled plasma optical emission spectroscopy, dynamic light scattering analysis, optical absorption and photoluminescence spectroscopy, and fluorescent imaging. The luminescence imaging region of the nanoprobe was extended to the near-infrared (NIR) (∼800 nm) by conjugation of the superparamagnetic nanoparticles with synthesized CdHgTe/CdS QDs. Cadmium, mercury based QDs in HINP can be easily replaced by novel water-soluble glutathione stabilized AgInS2/ZnS QDs to present a new class of cadmium-free multimodal imaging agents. The observed NIR photoluminescence of fluorescent magnetic nanocomposites supports their use for bioimaging. The developed HINP provides dual-imaging channels for simultaneous optical and magnetic resonance imaging.


Lactulose-mannitol intestinal permeability test in children with diarrhea caused by rotavirus and cryptosporidium. Diarrhea Working Group, Peru.
The relationship between intestinal permeability and acute secretory diarrheal syndromes caused by rotavirus and Cryptosporidium parvum in infants less than 36 months of age was studied using the lactulose-mannitol excretion assay. An oral solution containing 0.4 g/kg lactulose and 0.1 g/kg mannitol was administered to 15 infants with rotavirus, 7 with Cryptosporidium infection and a control group of 7 with secretory diarrhea admitted to the Oral Rehydration Unit of the National Children's Hospital in Lima, Peru. Urinary sugar excretion was measured using an enzymatic spectrophotometric method. The ratio of urinary excretion of lactulose to mannitol was used to measure intestinal mucosal permeability, with higher ratios indicative of increased intestinal permeability. Infants in all three groups were retested 20 days after the initial test. The (mean +/- SE) lactulose:mannitol (L:M) excretion ratios during the acute phase (day 1) of diarrhea in infants with rotavirus or Cryptosporidium and control infants were 0.67 +/- 0.1, 0.76 +/- 0.16, and 0.26 +/- 0.04, respectively. In the convalescent phase (day 20) the ratios were 0.19 +/- 0.02, 0.28 +/- 0.05, and 0.29 +/- 0.07, respectively. Significant reductions in L:M ratios were noted in rotavirus patients between days 1 and 20 (paired t-test; P < 0.01), Cryptosporidium patients between days 1 and 20 (paired t-test; P < 0.05), and between control subjects on day 1 and rotavirus patients on day 1 and Cryptosporidium patients on day 1 (unpaired t-tests; P < 0.05 for both). There were no significant differences in control subjects between days 1 and 20, control subjects and rotavirus patients on day 20, or control subjects and Cryptosporidium patients on day 20. The results indicate that increased intestinal permeability caused by rotavirus or cryptosporidium infections in Peruvian infants less than 36 months of age is a significant but reversible phenomenon. The temporal relationship observed in the current study and the contribution of such alterations in intestinal mucosal integrity to the burden of diarrheal disease and the development of malnutrition in developing countries is discussed.


Slit neuronal secretion coordinates optic lobe morphogenesis in Drosophila.
The complexity of the nervous system requires the coordination of multiple cellular processes during development. Among them, we find boundary formation, axon guidance, cell migration and cell segregation. Understanding how different cell populations such as glial cells, developing neurons and neural stem cells contribute to the formation of boundaries and morphogenesis in the nervous system is a critical question in neurobiology. Slit is an evolutionary conserved protein essential for the development of the nervous system. For signaling, Slit has to bind to its cognate receptor Robo, a single-pass transmembrane protein. Although the Slit/Robo signaling pathway is well known for its involvement in axon guidance, it has also been associated to boundary formation in the Drosophila visual system. In the optic lobe, Slit is expressed in glial cells, positioned at the boundaries between developing neuropils, and in neurons of the medulla ganglia. Although it has been assumed that glial cells provide Slit to the system, the contribution of the neuronal expression has not been tested. Here, we show that, contrary to what was previously thought, Slit protein provided by medulla neurons is also required for boundary formation and morphogenesis of the optic lobe. Furthermore, tissue specific rescue using modified versions of Slit demonstrates that this protein acts at long range and does not require processing by extracellular proteases. Our data shed new light on our understanding of the cellular mechanisms involved in Slit function in the fly visual system morphogenesis.


Behavioural changes and the adaptive diversification of pigeons and doves.
What factors determine the extent of evolutionary diversification remains a major question in evolutionary biology. Behavioural changes have long been suggested to be a major driver of phenotypic diversification by exposing animals to new selective pressures. Nevertheless, the role of behaviour in evolution remains controversial because behavioural changes can also retard evolutionary change by hiding genetic variation from selection. In the present study, we apply recently implemented Ornstein-Uhlenbeck evolutionary models to show that behavioural changes led to associated evolutionary responses in functionally relevant morphological traits of pigeons and doves (Columbiformes). Specifically, changes from terrestrial to arboreal foraging behaviour reconstructed in a set of phylogenies brought associated shorter tarsi and longer tails, consistent with functional predictions. Interestingly, the transition to arboreality accelerated the rates of evolutionary divergence, leading to an increased morphological specialization that seems to have subsequently constrained reversals to terrestrial foraging. Altogether, our results support the view that behaviour may drive evolutionary diversification, but they also highlight that its evolutionary consequences largely depend on the limits imposed by the functional demands of the adaptive zone.


[Effects of MSF on melanocyte adhesion and migration in vitro].
To investigate the Malytea Scurfpea fruit (MSF) on melanocyte adhesion and migration. Human epidermal melanocytes were treated with MSF and Ginger respectively, then adhesion to bovine serum fibronectin-coated culture dishes was checked. Control and treated cells were also examined for migration into micropore filters coated with the same protein. Compared with control, MSF treated melanocytes were obviously easier to adhere to the dishes and move into the filters in a dose-dependent manner. When the dose of MSF was 200 mg x L(-1), it could not reincrease melanocyte adhesion and migration. At 10 mg x L(-1), under every other concentrations of MSF, there was no marked difference among MSF-treated, Ginger-treated and untreated melanocytes (P < 0.05) when adhesion test were studied. But to migration, even at 10 mg x L(-1) MSF, there was obvious increased migration compared with MSF-untreated or Ginger-treated melanocytes (P < 0.01). MSF has effect on melanocyte adhesion and migration, which can explain, in part, the capacity of MSF to modulate melanocyte function in vitiligo lesions.


In vivo study of alginate hydrogel conglutinating cells to polycaprolactone vascular scaffolds fabricated by electrospinning.
The aim of this study was to explore an innovative cell-seeding technology applied on artificial vascular scaffolds. Scaffolds were fabricated by electrospinning polycaprolactone (PCL) and seeded with rat endothelial progenitor cells differentiated from adipose-derived stem cells. Then, we modified the PCL scaffolds through the use of alginate hydrogel conglutinating cells (AHCC), a blank alginate hydrogel coating (BAHC), and natural sedimentation seeding cells (NSSC). The blank PCL (BP) scaffolds without any modifications were considered the blank control group. After modification, the scaffolds were implanted in a rat model. The implanted scaffolds were harvested and observed using histological and immunohistochemical methods and scanning electron microscopy (SEM) at 1, 2, and 4 weeks after implantation, respectively. The best regeneration and configuration of the endothelium tissue and the most similar morphology to that of natural endangium was observed qualitatively in the AHCC scaffolds. The BP scaffolds had qualitatively the worst regeneration and configuration and the most dissimilar morphology at the same time point. In the AHCC group, cells could adhere directly on the inner surface of the vascular scaffolds, eliminating the time delay via the NSSC method prior to cell adhesion. AHCC are an effective method for seeding cells on vascular scaffolds and can eliminate the time delay for cell adhesion. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2443-2454, 2017.


Product inhibition of the fermentative formation of glutamic acid.
The addition of penicillin to cells of Corynebacterium glutamicum growing in 5-liter fermentors initiated the excretion of glutamic acid. The rate of glutamate production in fermentors declined continuously with time and reached 75% of the initial rate in 24 hr after penicillin had been added. The addition of glutamate to resting cell suspensions had only a slight effect on sugar utilization but caused a marked decrease in glutamate excretion. It is suggested that the high level of glutamate accumulating in the fermentation broth is responsible for inhibiting its own production.


Binge drinking alcohol and circadian misalignment in night shift nurses is associated with decreased resiliency to COVID-19 infection.
Nurses and other first responders are at high risk of exposure to the SARS-CoV2 virus, and many have developed severe COVID-19 infection. A better understanding of the factors that increase the risk of infection after exposure to the virus could help to address this. Although several risk factors such as obesity, diabetes, and hypertension have been associated with an increased risk of infection, many first responders develop severe COVID-19 without established risk factors. As inflammation and cytokine storm are the primary mechanisms in severe COVID-19, other factors that promote an inflammatory state could increase the risk of COVID-19 in exposed individuals. Alcohol misuse and shift work with subsequent misaligned circadian rhythms are known to promote a pro-inflammatory state and thus could increase susceptibility to COVID-19. To test this hypothesis, we conducted a prospective, cross-sectional observational survey-based study in nurses using the American Nursing Association network. We used validated structured questionnaires to assess alcohol consumption (the Alcohol Use Disorders Identification Test) and circadian typology or chronotype (the Munich Chronotype Questionnaire Shift -MCTQ-Shift). By latent class analysis (LCA), high-risk features of alcohol misuse were associated with a later chronotype, and binge drinking was greater in night shift workers. The night shift was associated with more than double the odds of COVID-19 infection of the standard shift (OR 2.67, 95% CI: 1.18 to 6.07). Binge drinkers had twice the odds of COVID-19 infection of those with low-risk features by LCA (OR: 2.08, 95% CI: 0.75 to 5.79). Working night shifts or binge drinking may be risk factors for COVID-19 infection among nurses. Understanding the mechanisms underlying these risk factors could help to mitigate the impact of COVID-19 on our at-risk healthcare workforce.


The putative heme transporter HCP1 is expressed in cultured astrocytes and contributes to the uptake of hemin.
Hemin, which is toxic to brain cells, has been reported to be taken up by cultured astrocytes; however, the mechanism of uptake is currently unknown. The present study investigated the mechanism of hemin uptake by rat primary astrocyte cultures. In medium containing 10% fetal calf serum, cultured astrocytes failed to accumulate significant amounts of heme-iron, while in serum-free medium the accumulation of heme-iron was found to be time- and concentration-dependent. After 6 h of incubation with 24 muM hemin, cells contained 36.2 +/- 2.4 nmol heme-iron/mg protein, which was 21% of the applied hemin. These results suggest that the accumulation of hemin in astrocytes does not require serum proteins such as hemopexin. A potential mechanism of hemin uptake in astrocytes involves the heme carrier protein 1 (HCP1), which is reported to mediate hemin uptake into intestinal cells. RT-PCR analysis revealed that astrocyte cultures contained HCP1 mRNA, and immunocytochemical staining and Western blot analysis confirmed the expression of HCP1 protein in cultured astrocytes. The functionality of HCP1 in astrocytes was demonstrated by incubating cells with zinc protoporphyrin IX (ZnPPIX), which is known to be transported into cells via HCP1, and ZnPPIX autofluorescence was detected in HCP1-positive astrocytes. In addition, ZnPPIX was found to attenuate the accumulation of heme-iron by astrocytes. These results are the first to demonstrate that cultured astrocytes contain functional HCP1 and that this transporter contributes to hemin uptake by astrocytes. HCP1 may therefore provide a new target for reducing hemin-related toxicity in brain cells.


Polymorphism in the Yersinia LcrV Antigen Enables Immune Escape From the Protection Conferred by an LcrV-Secreting Lactococcus Lactis in a Pseudotuberculosis Mouse Model.
Yersinioses caused by Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica are significant concerns in human and veterinary health. The link between virulence and the potent LcrV antigen has prompted the latter's selection as a major component of anti-Yersinia vaccines. Here, we report that (i) the group of Yersinia species encompassing Y. pestis and Y. pseudotuberculosis produces at least five different clades of LcrV and (ii) vaccination of mice with an LcrV-secreting Lactococcus lactis only protected against Yersinia strains producing the same LcrV clade as that of used for vaccination. By vaccinating with engineered LcrVs and challenging mice with strains producing either type of LcrV or a LcrV mutated for regions of interest, we highlight key polymorphic residues responsible for the absence of cross-protection. Our results show that an anti-LcrV-based vaccine should contain multiple LcrV clades if protection against the widest possible array of Yersinia strains is sought.


Hormonal regulation of protein phosphorylation in isolated rat heart cells.
We used a recently developed preparation of calcium-tolerant isolated rat cardiac ventricular cells to investigate certain aspects of hormone-mediated protein phosphorylation in heart tissue. Isoproterenol or dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) promoted the phosphorylation of at least 13 proteins and promoted the dephosphorylation of a single protein of relative molecular weight (Mr) 21,000, whose phosphorylation appeared to be stimulated by insulin. The isoproterenol-induced protein phosphorylations reached maximum levels for most proteins within 5 min at slightly different rates. However, when excess propranolol was added to the cells after exposure to isoproterenol, there appeared to be two major patterns of dephosphorylation: proteins that remained fully phosphorylated after propranolol addition, exemplified by proteins tentatively identified as troponin I and C-protein, and proteins that were rapidly dephosphorylated after propranolol, exemplified by phospholamban, the modulator of the sarcoplasmic reticulum calcium-dependent ATPase. The Mr 21,000 protein was rapidly dephosphorylated in response to isoproterenol and was rephosphorylated after addition of propranolol. This protein remains unidentified; it is not the Mr 19,000 myosin light chain whose phosphorylation state was unaffected by isoproterenol. This preparation of isolated heart cells provides a convenient way to investigate the biochemical effects resulting from exposure of the heart to hormones and can separate direct hormonal effects from those resulting from changes in contractility or heart rate.


Pediatric case reports: assessing recommendations from journals' instructions to authors.
Case reports (CRs) can be valuable contributions to medical knowledge and education. Objective assessments of publication potential and content recommendations for pediatric CRs are lacking. The "Instructions to Authors" provided by pediatric journals were assessed to determine journal characteristics, manuscript restrictions, and advice to writers. Pediatric journals referenced in the National Center for Biotechnology Information databases were identified by using the search term "pediatric." Further inclusion criteria were: active journals; currently indexed in the PubMed, Ovid, and/or Medline databases; and English as the primary language. Sixty-nine (52%) of 132 pediatric journals surveyed published CRs per their author instructions. The median 2011 impact factor for accepting journals was 1.28 (range: 0.47-5.44) compared with 2.40 (range: 0.59-5.50) for journals that did not publish CRs (P < .001). Twelve (67%) of 18 pediatric surgical specialty journals, 16 (55%) of 29 general pediatric journals, and 38 (51%) of 74 nonsurgical pediatric subspecialty journals published CRs. Sixteen journals had a separate Images section. Twenty-five (36%) of 69 journals provided no recommendations. Of the 44 journals that did provide recommendations, new insights/observations (64%) was the most common content recommendation, followed by clinical relevance (41%), novelty/rarity (39%), and instructive/educational value (32%). Approximately one-half of pediatric journals surveyed published CRs per their author instructions. Journals with lower impact factors were more likely to publish CRs. Many journals had specific formatting criteria. New insights and observations regarding relatively known pathology was the content criteria most often recommended.


Effect of imidazole and phenolate axial ligands on the electronic structure and reactivity of oxoiron(IV) porphyrin pi-cation radical complexes: drastic increase in oxo-transfer and hydrogen abstraction reactivities.
To study the effect of axial ligands on the electronic structure and reactivity of compound I of peroxidases and catalases, oxoiron(IV) porphyrin pi-cation radical complexes with imidazole, 2-methylimidazole, 4(5)-methylimidazole, and 3-fluoro-4-nitrophenolate as the axial ligands were prepared by ozone oxidation of iron(III) complexes of 5,10,15,20-tetramesitylporphyrin (TMP) and 2,7,12,17-tetramethyl-3,8,13,18-tetramesitylporphyrin (TMTMP). These complexes were fully characterized by absorption, (1)H, (2)H, and (19)F NMR, electron paramagnetic resonance (EPR), and electrospray ionization mass spectrometry (ESI-MS) spectroscopy. The characteristic absorption peak of compound I at approximately 650 nm was found to be a good marker for estimation of the electron donor effect from the axial ligand. The axial ligand effect did not change the porphyrin pi-cation radical state, the a(2u) state of the TMP complexes, or the a(1u) radical state of both the TMTMP complexes and compound I. The ferryl iron and porphyrin pi-cation radical spins were effectively transferred into the axial ligands for the a(2u) complexes but not for the a(1u) complexes. Most importantly, the reactivity of the oxoiron(IV) porphyrin pi-cation radical complex was drastically increased by the imidazole and phenolate axial ligands. The reaction rate for cyclooctene epoxidation was increased 100- to 400-fold with axial coordination of imidazoles and phenolate. A similar increase was also observed for the oxidation of 1,4-cyclohexadiene,N,N-dimethyl-p-nitroaniline and hydrogen peroxide. These results suggest extreme enhancement of the reactivity of compound I by the axial ligand in heme enzymes. The functional role of axial ligands on the compound I in heme enzymes is discussed.


Selective nitration of Tyr99 in calmodulin as a marker of cellular conditions of oxidative stress.
We examined the possible role of methionines as oxidant scavengers that prevent the peroxynitrite-induced nitration of tyrosines within calmodulin (CaM). We used mass spectrometry to investigate the reactivity of peroxynitrite with CaM at physiological pH. The possible role of methionines in scavenging peroxynitrite (ONOO-) was assessed in wild-type CaM and following substitution of all nine methionines in CaM with leucines. We find that peroxynitrite selectively nitrates Tyr99 at physiological pH, resulting in the formation of between 0.05 and 0.25 mol of nitrotyrosine/mol of CaM when the added molar ratio of peroxynitrite per CaM was varied between 2.5 and 1.5. In wild-type CaM there is a corresponding oxidation of between 0.8 and 2.8 mol of methionine to form methionine sulfoxide. However, following site-directed substitution of all nine methionines in wild-type CaM with leucines, the extent of nitration by peroxynitrite was unchanged. These results indicate that Tyr99 is readily nitrated by peroxynitrite and that methionine side chains do not function as an antioxidant in scavenging peroxynitrite. Thus, separate reactive species are involved in the oxidation of methionine and nitration of Tyr99 whose relative concentrations are determined by solution conditions. The sensitivity of Tyr99 in CaM to nitration suggests that CaM-dependent signaling pathways are sensitive to peroxynitrite formation and that nitration of CaM represents a cellular marker of peroxynitrite-induced changes in cellular function.


A Retrospective Comparative Analysis of Titanium Mesh and Custom Implants for Cranioplasty.
Autologous bone removed during craniectomy is often the material of choice in cranioplasty procedures. However, when the patient's own bone is not appropriate (infection and resorption), an alloplastic graft must be utilized. Common options include titanium mesh and polyetheretherketone (PEEK)-based custom flaps. Often, neurosurgeons must decide whether to use a titanium or custom implant, with limited direction from the literature. To compare surgical outcomes of synthetic cranioplasties performed with titanium or vs custom implants. Ten-year retrospective comparison of patients undergoing synthetic cranioplasty with titanium or custom implants. A total of 82 patients were identified for review, 61 (74.4%) receiving titanium cranioplasty and 21 (25.6%) receiving custom implants. Baseline demographics and comorbidities of the 2 groups did not differ significantly, although multiple surgical characteristics did (size of defect, indication for craniotomy) and were controlled for via a 2:1 mesh-to-custom propensity matching scheme in which 36 titanium cranioplasty patients were compared to 18 custom implant patients. The cranioplasty infection rate of the custom group (27.8%) was significantly greater (P = .005) than that of the titanium group (0.0%). None of the other differences in measured complications reached significance. Discomfort, a common cause of reoperation in the titanium group, did not result in reoperation in any of the patients receiving custom implants. Infection rates are higher among patients receiving custom implants compared to those receiving titanium meshes. The latter should be informed of potential postsurgical discomfort, which can be managed nonsurgically and is not associated with return to the operating room.


American Nursing Informatics Association role survey.
A descriptive study, using a survey approach, was conducted among 48 American Nursing Informatics Association (ANIA) member respondents to determine the nursing informatics role among professional nurses working in the specialty. Members were asked to complete a survey regarding their current position, educational and work experience, continuing education, and work challenges. Although the ages of the informatics nurses parallel the national, range, most have been in the field of nursing informatics for 2.5 to 5 years and in their current position only 1.5 to 2 years. Job responsibilities and challenges indicate common issues and concerns that have implications for the specialty of nursing informatics and nursing in general.


Differential expression of CYP1A1 and CYP1B1 in human breast epithelial cells and breast tumor cells.
Human cytochromes P450 1A1 (CYP1A1) and P450 1B1 (CYP1B1) catalyze the metabolic activation of a number of procarcinogens and the hydroxylation of 17beta-estradiol (E2) at the C-2 and C-4 positions, respectively. The aromatic hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a marked effect on estrogen metabolism in MCF-7 breast-tumor cells by induction of these two enzymes. To investigate whether induction of CYP1A1 and CYP1B1 by AhR agonists and the associated increase in E2 metabolism are common to all breast epithelial cells and breast-tumor cells, we determined the effects of TCDD on E2 metabolism, and CYP1A1 and CYP1B1 mRNA levels in a series of non-tumor-derived breast epithelial (184A1 and MCF-10A) and breast-tumor (MCF-7, T-47D, ZR-75-1, BT-20, MDA-MB-157, MDA-MB-231 and MDA-MB-436) cell lines. In 184A1 cells, which did not express detectable estrogen receptor (ER) alpha mRNA, CYP1A1 mRNA and activity were induced by TCDD, and enhanced E2 metabolism in TCDD-treated cells was predominantly E2 2-hydroxylation. In MCF-10A, MCF-7, T-47D, ZR-75-1 and BT-20 cells, which expressed varying levels of ER alpha mRNA, both CYP1A1 and CYP1B1 mRNA levels and rates of both E2 2- and 4-hydroxylation were highly elevated following exposure to TCDD. In MDA-MB-157, MDA-MB-231 and MDA-MB-436 cells, which did not express detectable ER alpha mRNA and generally displayed fibroblastic or mesenchymal rather than epithelial morphology, CYP1B1 induction was favored, and the rate of E2 4-hydroxylation exceeded that of 2-hydroxylation in TCDD-treated cells. These results show that breast epithelial cells and tumor cells vary widely with regard to AhR-mediated CYP1A1 and CYP1B1 induction, suggesting that factors in addition to the AhR regulate CYP1A1 and CYP1B1 gene expression. In these cell lines, significant CYP1A1 inducibility was restricted to cultures displaying epithelial morphology, whereas CYP1B1 inducibility was observed in cells of both epithelial and mesenchymal morphology.


Symptoms of Depression and Preterm Birth Among Black Women.
To investigate the relationship between depressive symptoms and preterm birth (PTB) while adjusting for social support, both general and from the father of the baby. Retrospective study design. Participants of the Life-course Influences of Fetal Environments (LIFE) study were recruited from a suburban hospital in Metropolitan Detroit, Michigan. The LIFE data consisted of 1,410 self-identified Black women age 18 to 45 years; 1,207 women were included in this analysis. Women were interviewed using a structured questionnaire administered 24 to 48 hours after birth during their postpartum hospitalization. Data on the newborns and their mothers' health were collected through medical record abstraction. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure symptoms of depression. The CES-D scores ≥23 were considered severe symptoms of depression. Modified Poisson regression models were built using a stepwise approach to assess association between symptoms of depression and PTB. Approximately, 17% of women had a PTB and 20% of women in the sample had a CES-D scores ≥23. Women who had CES-D score ≥23 were about 70% more likely to have a PTB compared with women with CES-D scores <23 (PR = 1.68, 95% CI: 1.24-2.16) after adjustment for both general social support and father of the baby support. Women with CES-D scores ≥23 were almost twice more likely to have PTB compared with women with CES-D scores <23. Referrals for mental healthcare providers might benefit women with symptoms of depression and improve birth outcomes. Nurses should encourage women to seek support beyond the father of the baby.


Schema and parental bonding in overweight and nonoverweight female adolescents.
To investigate whether family functioning and cognitions in a group of overweight female adolescents differ significantly from those in a group of normal weight female adolescents. Cross-sectional study. In all, 23 overweight female adolescents (mean age: 17.6 y, mean body mass index (BMI: 27.8 kg/m2), and 23 normal weight female adolescents (mean age: 17.7 y, mean BMI: 20.2 kg/m2). The following self-report measures were completed: the Parental Bonding Inventory, the Young Schema Questionnaire-short version, the Eating Attitudes Test, the Beck Depression Inventory and the Eating Disorder Belief Questionnaire. Overweight female adolescents reported more negative self-beliefs and greater belief in schema relating to emotional deprivation, fears of abandonment, subjugation and insufficient self-control. They also perceived their fathers as being significantly more overprotective and significantly less caring. Within this group perceived level of maternal care correlated negatively with negative self-beliefs and schema. Overweight female adolescents show some of the cognitive features associated with the development of an eating disorder. However, positive parent-child relationships may serve to protect overweight adolescents from developing clinical eating disorders and from psychological distress later in life.


Association between medical student debt and choice of specialty: a 6-year retrospective study.
The effect of rapidly increasing student debt on medical students' ultimate career plans is of particular interest to residency programs desiring to enhance recruitment, including primary care specialties. Previous survey studies of medical students indicate that amount of student debt influences choice of medical specialty. Research on this topic to date remains unclear, and few studies have included the average income of different specialties in analyses. The purpose of this study is to observe whether empirical data demonstrates an association between debt of graduating medical students and specialties into which students match. This was a retrospective cross-sectional study of a public institution including data from graduation years 2010-2015. For each included student, total educational debt at graduation and matched specialty were obtained. Average income of each specialty was also obtained. Statistical hypothesis testing was performed to analyze any differences in average debt among specialties; subanalysis was performed assessing debt for primary care (PC) versus non-primary care (NPC) specialties. Correlation between student debt and average specialty income was also evaluated. One thousand three hundred ten students met the inclusion criteria and 178 were excluded for a final study population of 1132 (86%). The average debt was $182,590. Average debt was not significantly different among the different specialties (P = 0.576). There was no significant difference in average debt between PC and NPC specialties (PC $182,345 ± $64,457, NPC $182,868 ± $70,420, P = 0.342). There was no correlation between average specialty income and graduation debt (Spearman's rho = 0.021, P = 0.482). At our institution, student indebtedness did not appear to affect matched medical specialty, and no correlation between debt and average specialty income was observed. Different subspecialties and residency programs interested in recruiting more students or increasing diversity may consider addressing alternative factors which may have a stronger influence on student choices.


Calcineurin is required for virulence of Cryptococcus neoformans.
Cyclosporin A (CsA) and FK506 are antimicrobial, immunosuppressive natural products that inhibit signal transduction. In T cells and Saccharomyces cerevisiae, CsA and FK506 bind to the immunophilins cyclophilin A and FKBP12 and the resulting complexes inhibit the Ca2+-regulated protein phosphatase calcineurin. We find that growth of the opportunistic fungal pathogen Cryptococcus neoformans is sensitive to CsA and FK506 at 37 degrees C but not at 24 degrees C, suggesting that CsA and FK506 inhibit a protein required for C. neoformans growth at elevated temperature. Genetic evidence supports a model in which immunophilin-drug complexes inhibit calcineurin to prevent growth at 37 degrees C. The gene encoding the C. neoformans calcineurin A catalytic subunit was cloned and disrupted by homologous recombination. Calcineurin mutant strains are viable but do not survive in vitro conditions that mimic the host environment (elevated temperature, 5% CO2 or alkaline pH) and are no longer pathogenic in an animal model of cryptococcal meningitis. Introduction of the wild-type calcineurin A gene complemented these growth defects and restored virulence. Our findings demonstrate that calcineurin is required for C. neoformans virulence and may define signal transduction elements required for fungal pathogenesis that could be targets for therapeutic intervention.


One night of sleep deprivation affects reaction time, but not interference or facilitation in a Stroop task.
The Stroop color-naming task is one of the most widely studied tasks involving the inhibition of a prepotent response, regarded as an executive function. Several studies have examined performance on versions of the Stroop task under conditions of acute sleep deprivation. Though these studies revealed effects on Stroop performance, the results often do not differentiate between general effects of sleep deprivation on performance and effects specifically on interference in the Stroop task. To examine the effect of prolonged wakefulness on performance on the Stroop task, we studied participants in a 40-h "constant routine" protocol during which they remained awake in constant conditions and performed a Stroop color-naming task every two hours. We found that reaction time was slowest when the color and word did not match (incongruent), fastest when the color and word did match (congruent), and intermediate when participants named the color of the non-word stimulus (neutral). Performance on all three trial types degraded significantly as a function of time awake. Extended wakefulness did not significantly change the additional time needed to respond when the color and word did not match (Stroop interference), nor did it change the amount of facilitation when color and word matched. These results indicate that one night of sleep deprivation influences performance on the Stroop task by an overall increase in response time, but does not appear to impact the underlying processes of interference or facilitation. The results suggest that the degree to which an "executive function" is affected by sleep deprivation may depend on the particular executive function studied and the degree to which it is subserved by the prefrontal cortex.


Diagostic Accuracy of C4d-IHC in Diagnosis of MGN.
Membranous glomerulonephritis (MGN) is the most common cause of nephrotic syndrome in adults. The gold standard techniques for diagnosis of MGN are based on a constellation of findings given by light microscope, electron microscope (EM), and immunofluorescence (IF). Occasionally, only formalin-fixed tissues are available for the analysis by light microscopy, which have limitations in differentiating minimal change diseases from MGN. Recently, the usage of C4d immunohistochemistry (IHC) has been proposed for the diagnosis of MGN. The aim of this study was to evaluate the accuracy of C4d-IHC in diagnosis of MGN. The present investigation conducted on patients with nephrotic syndrome who underwent renal biopsy in Labbafinejad hospital, from 2016 to 2017. The entire specimens were examined by light microscope, immunofluorescence, and electron microscope as a gold standard method for diagnosis of MGN. The samples were then stained for C4d immunohistochemical analysis. Eventually, the sensitivity, specificity, positive, and negative predictive value for C4d-IHC was determined. The sensitivity and specificity of the C4d-IHC in order to differentiate MGN from other glomerulopathies were 95% and 87.5%, respectively. In addition, the negative and positive predictive values were 97.2% and 79.16%, respectively. It was ultimately attained that C4d-IHC has more accuracy in identification and diagnosis of MGN, in contrary to EM and IF, this method is more usable and cost effective, which requires a lower level of skill and advanced equipment. Indeed, this technique does not require fresh specimen.


Impact of psychological interventions on reducing anxiety, fear and the need for sedation in children undergoing magnetic resonance imaging.
Children undergoing magnetic resonance imaging examination frequently experience anxiety and fear before and during the scanning. The aim of the present study was to assess: i) whether and to what extent psychological interventions might reduce anxiety and fear levels; ii) whether the intervention is related to a decrease in the need for sedation. The interventions consisted of three activities: a clown show, dog interaction and live music. The emotional status (anxiety and fear) of the children was evaluated before and after the activities through a rating scale questionnaire. The results showed that the activities had high effectiveness in reducing the level of anxiety and fear and decreased the need for sedation in the experimental group compared to the control group. This approach proved to be a positive patient experience, helping to alleviate children's anxiety and fear, decreasing the need for sedation, and was cost-effective.


Determinants of postictal agitation and recovery after tonic-clonic seizures in generalized and focal epilepsy.
The postictal state after bilateral tonic-clonic seizures is often prolonged and can have significant impact on a patient's quality of life. Considerable variability exists in the magnitude of postictal agitation and in the speed of recovery, the determinants of which are not well understood. We studied postictal behavior after tonic-clonic seizures in various epilepsy localizations, focusing on postictal agitation and time to responsiveness. We retrospectively identified 15 adult patients each with idiopathic generalized, left temporal lobe, right temporal lobe and frontal lobe epilepsy. Localization in focal epilepsy was validated by good outcome after resective surgery at one-year of follow-up. The first tonic-clonic seizure with reliable video and EEG for each patient was analyzed by two reviewers, one of whom was blinded to clinical data. Clinical, ictal and postictal variables were collected for each patient and analyzed. Postictal agitation was classified as mild and marked. We reviewed 60 tonic-clonic seizures, 15 in each of four patient groups. Postictal agitation was observed in 14 patients (23.3%; marked in one and mild in 13). Postictal agitation was most common in patients with left temporal (seven patients) and least common in idiopathic generalized epilepsy (one patient) groups (p=0.035). Based on subgroup analysis (n=28), time to responsiveness was 6.6 minutes for frontal, 7.2 minutes for generalized, 10 minutes for right temporal and 15.7 minutes for the left temporal groups (p<0.05 for frontal vs. left temporal, generalized vs. left temporal). Time to responsiveness was longer in patients with agitation than without (13.9 minutes vs. 7.7 minutes; p=0.048). Patient ictal and postictal characteristics demonstrated no relationship to agitation or latency to postictal recovery. To mitigate harm, patients must be monitored carefully after tonic-clonic seizures, especially patients with left temporal lobe epilepsy. Studies evaluating medical and behavioral interventions to promote postictal recovery are needed.


[Clinical update in critical care of pulmonary medicine 2023].
This article reviewed the clinical progress in the field of pulmonary and critial care medicine, both domestically and internationally during the year 2023 (from October 1, 2022 to September 30, 2023). In 2023, there have been significant modifications to the global definition of Acute Respiratory Distress Syndrome (ARDS). These include the inclusion of SpO2/FiO2 as a diagnostic criterion for ARDS, the addition of parameters for high-flow nasal cannula humidified oxygen therapy as a basis for diagnosing ARDS in non-intubated patients, clarification of the need to diagnose ARDS in non-intubated patients with PEEP≥5 cmH2O under non-invasive positive pressure ventilation, and the increased diagnostic value of ultrasound. Bedside electrical impedance, transpulmonary pressure and severe ultrasound provide effective means for for individualized assessment of critically ill patients. End-tidal alveolar dead space fraction, intestinal microecological imbalance, and ICU-acquired weakness are important warning indicators for the prognosis of critically ill patients. Machine learning models based on big data can effectively predict the prognosis of critically ill patients, and ECMO combined with prone positioning can improve patient outcomes. Cognition and fatigue were the most common persistent symptoms in critically ill patients after discharge. Intervention on specific cellular subtypes of lung injury receptors may be a future target for personalized treatment of lung injury tissue repair.


PET/CT imaging in neuroblastoma.
123Iodine-metaiodobenzylguanidine (123I-MIBG) scintigraphy is currently the tracer of choice for neuroblastoma (NB). It has high diagnostic accuracy and prognostic value for the assessment of patients after chemotherapy. A positive 123I-MIBG scan is also used for the basis of targeted radionuclide therapy with 131I-MIBG. I-123 MIBG scan however has some limitations which should be taken into account. Moreover the reasons for false negative MIBG results have not been entirely elucidated. Meticulous correlation with radiological examinations and recognition of the normal distribution pattern of 123I-MIBG in children is vital to obtain optimal results. With its technical superiorities, positron emission tomography/computed tomography (PET/CT) can be successfully introduced into the diagnostic workup of NB. Different PET tracers have been offered for imaging in patients with NB, and the efficacy of this modality has been compared with that of 123I-MIBG scan. Our review aims to analyze the present role of PET/CT imaging and radiopharmaceuticals in NB.


The effect of gemigliptin treatment on immune parameters including regulatory T cells in patients with type 2 diabetes and moderate to very severe chronic renal impairment.
It is crucial to understand the impact of DPP-4 inhibitors on the immune system, particularly T cell differentiation, maturation, and proliferation, in patients with type 2 diabetes and CKD. This prospective observational study aimed to investigate the distribution of immune cells (particularly regulatory T cells), following the administration of gemigliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus and chronic kidney disease. We enrolled 28 patients with type 2 diabetes, aged 20 to 69, who had been taking a daily dose of 50mg gemigliptin for <3 months and had chronic kidney disease stages 3, 4, or 5, including that undergoing dialysis. T regulatory cells were defined as CD4 + CD25 high CD127 low/- FoxP3 + phenotype, and flow cytometry was used to examine the distribution of T regulatory cells. In the patient group, blood samples were collected at baseline, as well as at 3 and 6 months after initiating medication. Of the 28 patients, 17 (60.7%) were male and the mean age was 61.82 ± 8.03 years. Serum Cr ≥ 1.5 mg/dL was 16 (57%), and Cr < 1.5 mg/dL was 12 (43%). The number of CD4(+)/CD25(+) cells did not significantly increase or decrease in baseline, 3 months, and 6 months time changes, and the number of CD127(-/FoxP3(+) cells did not change significantly. Treatment with gemigliptin for 3 and 6 months did not significantly alter the number, percentage, or ratio of circulating Treg cells in patients with type 2 diabetes and CKD. Therefore, the administration of gemigliptin may help maintain regulatory T cells or have no significant impact.


Consideration of Occult Infection and Sepsis Mimics in the Sick Patient Without an Apparent Infectious Source.
Evaluation and treatment of the acutely ill patient is typically complicated by multiple comorbidities and incomplete medical histories. This is exemplified by patients with sepsis, whose care is complicated by variable presentations, shifting definitions, and a variety of potential sources. Many practitioners fail to consider and recognize less-common sources of infection in a timely manner. Additionally, multiple noninfectious conditions can present with the fever and tachycardia typical of the septic patient. The errors of anchoring and premature closure may lead to delay in, or failure of, diagnosis of these conditions. This review addresses the evaluation of the acutely ill-appearing patient without an apparent source, focusing on occult sources of infection and conditions that mimic sepsis. Musculoskeletal, cardiac, neuraxial, and abdominal sources of sepsis should be considered in the acutely ill patient. Indwelling devices should be carefully examined for signs of infection. Consideration for sepsis mimics, such as neuroleptic malignant syndrome, malignant hyperthermia, medication toxicity, and thyroid storm, in patients who fail to respond to standard therapies for sepsis, may lead the physician to potentially reversible life-threatening diagnoses and management. In the seemingly septic patient who does not respond to antimicrobials and fluids, the differential should be broadened to include acutely life-threatening conditions that can mimic sepsis. A review of the patient's medical history, medications, and recent exposures can assist in identifying the source of the patient's elevated body temperature and tachycardia. Consideration of potential sources and other mimics of sepsis is needed in the emergency department.


Diazepam Inhibits Proliferation of Lymph Node Cells Isolated from Rats with Experimental Autoimmune Encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease with similarities to human multiple sclerosis involving peripheral activation of autoreactive T cells which infiltrate the central nervous system and react to self antigens leading to damage. In previous studies, we have demonstrated that treatment with diazepam decreases the incidence and histological signs associated with the disease and diminishes immunological responses. The aim of the present work was to evaluate direct effects of diazepam on isolated T cells involved in immune responses during the development of EAE. Animals were sensitized with whole myelin to induce EAE and sacrificed during the acute phase of the disease. In mononuclear cells isolated from popliteal lymph nodes, cell viability, apoptosis induction, proliferation and cytokine production were evaluated. Diazepam did not have a toxic or proapoptotic effect on the cells, at least up to the concentration of 25 μM, but proliferation, CD8+ T-cell activation and proinflammatory cytokine production were dose-dependently decreased. Diazepam has a direct inhibitory effect on the proliferation and activation of T lymphocytes isolated from the main lymphoid organ involved in disease onset and this could be one of the mechanisms that contribute to the beneficial effect previously observed with diazepam in vivo during EAE development.


Exhaustive mining of EST libraries for genes differentially expressed in normal and tumour tissues.
A four-step procedure for the efficient and systematic mining of whole EST libraries for differentially expressed genes is presented. After eliminating redundant entries from the EST library under investigation (step 1), contigs of maximal length are built upon each remaining EST using about 4 000 000 public and proprietary ESTs (step 2). These putative genes are compared against a database comprising ESTs from 16 different tissues (both normal and tumour affected) to determine whether or not they are differentially expressed (step 3; electronic northern). Fisher's exact test is used to assess the significance of differential expression. In step 4, an attempt is made to characterise the contigs obtained in the assembly through database comparison. A case study of the CGAP library NCI_CGAP_Br1.1, a library made from three (well, moderately, and poorly differentiated) invasive ductal breast tumours (2126 ESTs in total) was carried out. Of the maximal contigs, 139 were found to be significantly (alpha = 0.05) over-expressed in breast tumour tissue, while 13 appeared to be down-regulated.


The Impact of Treatment Adherence for Patients With Diabetes and Hypertension on Cardiovascular Disease Risk: Protocol for a Retrospective Cohort Study, 2008-2018.
Cardiovascular disease (CVD) is the leading cause of death globally and in Canada. Diabetes and hypertension are major risk factors for CVD events. Despite the increasing availability of effective treatments, the majority of diabetic and hypertensive patients do not have adequate blood pressure and glycemic control. One of the major contributors is poor treatment adherence. This study aims to evaluate the impact of treatment adherence for patients with both diabetes and hypertension on acute severe CVD events and intermediate clinical outcomes in Canadian primary care settings. We will conduct a population-based retrospective cohort study of patients living with both diabetes and hypertension in Ontario, Canada, between January 1, 2008, and March 31, 2018. The Social Cognitive Theory will be used as a conceptual framework by which to frame the reciprocal relationship between treatment adherence, personal factors, and environmental determinants and how this interplay impacts CVD events and clinical outcomes. Data will be derived from the Diabetes Action Canada National Data Repository. A time-varying Cox proportional hazards model will be used to estimate the impacts of treatment adherence on CVD morbidity and mortality. Multivariable linear regression models and hierarchical regression models will be used to estimate the associations between treatment adherence of different medication categories and intermediate clinical outcomes. Our primary outcome is the association between treatment adherence and the risk of acute severe CVD events, including CVD mortality. The secondary outcome is the association between treatment adherence and intermediate clinical outcomes including diastolic and systolic blood pressures, glycated hemoglobin, low-density lipoprotein cholesterol, and total cholesterol. Owing to data limitation, we use medication prescriptions as a proxy to estimate treatment adherence. We assume that a patient adhered to medications if she or he had any prescription record in the 4 preceding quarters and 1 quarter after each quarter of interest. Acute severe CVD events are defined based on the World Health Organization's Monitoring Trends and Determinants in Cardiovascular Disease Project, including acute coronary heart disease, stroke, and heart failure. As causes of death are not available, the number of CVD deaths will be computed using the most recent systolic blood pressure distributions and the population attributable risks related to systolic blood pressure level. The project was funded by Diabetes Action Canada (reference number: 503854) and approved by the University of Toronto Research Ethics Board (reference number: 36065). The project started in June 2018 and is expected to be finished by September 2019. The findings will be helpful in identifying the challenges of treatment adherence for diabetic and hypertensive patients in primary care settings. This will also help to develop intervention strategies to promote treatment adherence for patients with multi-morbidities. DERR1-10.2196/13571.


Capstan friction model for DNA ejection from bacteriophages.
Bacteriophages infect cells by attaching to the outer membrane and injecting their DNA into the cell. The phage DNA is then transcribed by the cell's transcription machinery. A number of physical mechanisms by which DNA can be translocated from the phage capsid into the cell have been identified. A fast ejection driven by the elastic and electrostatic potential energy of the compacted DNA within the viral capsid appears to be used by most phages, at least to initiate infection. In recent in vitro experiments, the speed of DNA translocation from a λ phage capsid has been measured as a function of ejected length over the entire duration of the event. Here, a mechanical model is proposed that is able to explain the observed dependence of exit velocity on ejected length, and that is also consistent with the accepted picture of the geometric arrangement of DNA within the viral capsid.


Perspective: the case for subspecialty clinical learning in early medical education-moving from case-based to patient-based learning.
The subspecialty departments are greatly underutilized for teaching during the first two years of medical school. While second-year students are spending most of their time behind closed doors in the laboratory, lectures, and small groups, the clinical environment is teeming with actual patients whose cases are often directly analogous to the material being learned. Moreover, even in today's environment of increased emphasis on quality of medical care and medical education reform, many U.S. medical students still lack essential exposure to common technologies, tests, and procedures performed within several subspecialties. To remedy this situation, the authors propose that educators develop a system of subspecialty clinical learning for first- and/or second-year students correlated to the classroom study of the pathophysiology of the various organ systems. For example, the second-year cardiology course could be augmented with self-directed, patient-centered learning assignments in the cardiac unit, the pathology lab, the echo lab, and other areas. The authors explain the several advantages of comprehensive subspecialty clinical learning (e.g., it will help prepare physicians to practice distributed care, aid development of competencies within the behavioral and social sciences, foster students' professional development, and encourage creative approaches to issues of health care quality). The authors acknowledge the multiple difficulties of implementing such an approach, and present evidence supporting their argument that with the appropriate vision and leadership, such a living curriculum is important and achievable.