Considerations regarding adherence of anti-osteoporosis therapy.
Osteoporosis remains a challenging disease to treat due to a number of barriers including patient adherence to therapies. One of the most recent advances has been the development of the Fracture Risk Assessment Tool, which is helpful in conveying fracture risk to patients and providing treatment guidance to clinicians. The decision to use an anti-osteoporosis therapy must be tailored to the patient's specific clinical scenario. The bisphosphonates are first-line agents in the treatment of osteoporosis and are efficacious in substantially reducing fracture risk between 25% and 70% on average depending on fracture site. Compliance with oral bisphosphonate pills can be poor, resulting in a significant deterrent to the proper management of osteoporosis. Non-pill forms of bisphosphonate and nonbisphosphonate therapy are available for the treatment of osteoporosis and may increase compliance. Among these is Binosto, a new formulation of weekly effervescent alendronate, as well as intravenous bisphosphonates, teriparatide, and subcutaneously administered denosumab, which are all costly medications and are unlikely to become the mainstay of treatment over the oral bisphosphonate pills. Having a detailed conversation between the patient and physician is essential to the development of a tailored treatment plan that will decrease fracture risk.


Emotion recognition and false belief in deaf or hard-of-hearing preschool children.
This study aims to examine emotion recognition and false belief performances of 4-5-year-old (48-71 months) deaf or hard-of-hearing (DHH) children. The performances have been assessed using the Turkish Version of the Theory of Mind Task Battery for Children. The DHH children have been continuing schooling in inclusive settings with an auditory-oral approach. The emotion recognition performances of hearing children (n = 100) and DHH (n = 100) children have appeared to be similar. The ANOVA analysis has revealed that the groups do not differ concerning false belief performances between the ages of 4 and 5.5. However, from the age of 5.5, hearing children have performed better than DHH children. According to correlation analysis, parental education has been determined as a remarkable factor in DHH children's false belief development. The findings point to the need for research across a wide range of ages to better understand the developmental course of false belief in DHH children.


Evaluating the long-term persistence of Bacillus spores on common surfaces.
Bacillus spores resist inactivation, but the extent of their persistence on common surfaces is unclear. This work addresses knowledge gaps regarding biothreat agents in the environment to reduce uncertainty in risk assessment models. Studies were conducted to investigate the long-term inactivation of Bacillus anthracis and three commonly used surrogate organisms - B. cereus, B. atrophaeus and B. thuringiensis on three materials: laminate countertop, stainless steel and polystyrene Petri dishes. Viable spores were measured at 1, 30, 90, 196, 304 and 1038 days. Twelve different persistence models were fit to the data using maximum likelihood estimation and compared. The study found that (1) spore inactivation was not log-linear, as commonly modelled; (2) B. thuringiensis counts increased at 24 h on all materials, followed by a subsequent decline; (3) several experiments showed evidence of a 'U' shape, with spore counts apparently decreasing and then increasing between 1 and 304 days; (4) spores on polystyrene showed little inactivation; and (5) the maximum inactivation of 56% was observed for B. atrophaeus spores on steel at 196 days. Over the range of surfaces, time durations and conditions (humidity controlled vs. uncontrolled) examined, B. thuringiensis most closely matched the behaviour of B. anthracis.


Elevated blood carboxyhemoglobin levels as an early predictor of phototherapy requirement in moderate and late preterm infants.
Objective: Preterm infants are prone to increased bilirubin burden and display adverse outcomes if left unmonitored; therefore, predicting an increased bilirubin production is of paramount importance.Methods: We aimed to evaluate carboxyhemoglobin (COHb) levels in moderate (GA: 320/7-336/7) and late preterm (GA: 340/7-366/7) infants to assess whether this molecule could be used as an early predictor of phototherapy requirement.Results: A total of 221 infants were enrolled in the study. On admission, carboxyhemoglobin levels of infants who received phototherapy were significantly higher than that of infants who did not require this treatment, and this difference persisted in the consecutive hours (median (min-max): 1.2% (0.3-1.7) versus 0.8% (0.4-1.1); p < .001). The initial and consecutive COHb levels showed positive correlation (r = 0.77, p < .001). In the post-hoc analysis, direct antiglobulin test positivity significantly affected phototherapy requirement (p < .001). Receiver operating characteristics analysis showed that a COHb level of ≥0.95% was found to have a sensitivity of 90% and a specificity of 88%. Multinomial logistic regression analysis demonstrated that high COHb levels on admission significantly increased the likelihood of phototherapy requirement when adjusted for covariants (adjusted odds ratio: 2.2; 95% confidence interval: 1.4-3.5; p < .001).Conclusion: Carboxyhemoglobin measurement can be simply used to predict preterm infants who will require phototherapy.


[The chronotropic effect of maximal stress on the heart and its regulation].
The reflex bradycardia occurring at the maximal isometric heart strain produced by clamping of aorta was shown to be less intense if the heart rate prior to the experiment had been low. Vagotomy prevented or decreased the bradycardia. The beta-adrenoreceptor blockade with inderal significantly reduced the bradycardia, whereas the alpha-adrenoreceptor blockade with tropaphen increased it. The important role of relationship between adrenergic and cholinergic regulation of the heart in development of the bradycardia was discussed.


The hip-spine connection: understanding its importance in the treatment of hip pathology.
EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Discuss the kinematic relationship between the hip and lumbar spine. 2. Explain the innervation of the hip and lumbar spine and how they relate to one another. 3. Recognize the effect of hip disease on the lumbar spine in an athletic population, prior to the onset of degenerative changes. 4. Describe an algorithm for diagnosis and treatment of patients who present with concomitant hip and lumbar spine pain. The hip and lumbar spine are closely related and can create similar patterns of pain and dysfunction. Diagnosis and treatment of hip and spine-related conditions can be challenging due to symptom overlap. Successful evaluation and treatment of hip and lumbar spine conditions requires a thorough understanding the hip-spine connection. Historically the hip-spine connection has been considered in the context of arthrosis; however, the hip-spine connection also needs to be considered in a younger athletic population. The purpose of this review is to describe the hip-spine connection, discuss the clinical implications of this connection, and offer an approach to diagnosis and treatment.


Are Everolimus-Eluting Stents Associated With Better Clinical Outcomes Compared to Other Drug-Eluting Stents in Patients With Type 2 Diabetes Mellitus?: A Systematic Review and Meta-Analysis.
Controversies still exist with the use of Everolimus-Eluting Stents (EES) compared to other Drug-Eluting Stents (DES) in patients with Type 2 Diabetes Mellitus (T2DM). Therefore, in order to solve this issue, we aim to compare the 1-year adverse clinical outcomes between EES and non-EE DES with a larger number of patients with T2DM.Medline, EMBASE, PubMed databases, as well as the Cochrane library were searched for randomized controlled trials (RCTs) and observational studies (OS) comparing EES and non-EE DES in patients with T2DM. One-year adverse outcomes were considered as the clinical endpoints in this study. Odd ratios (OR) with 95% confidence interval (CI) were used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3.Ten studies consisting of a total of 11,981 patients with T2DM (6800 patients in the EES group and 5181 in the non-EE DES group) were included in this meta-analysis. EES were associated with a significantly lower major adverse cardiac events (MACEs) with OR: 0.83, 95% CI: 0.70-0.98, P = 0.03. Revascularization including target vessel revascularization (TVR) and target lesion revascularization (TLR) were also significantly lower in the EES group with OR: 0.62, 95% CI: 0.40-0.94, P = 0.03 and OR: 0.74, 95% CI: 0.57-0.95, P = 0.02, respectively. Also, a significantly lower rate of stent thrombosis with OR: 0.63, 95% CI: 0.46-0.86, P = 0.003 was observed in the EES group. However, a similar mortality rate was reported between the EES and non-EE DES groups.During this 1-year follow-up period, EES were associated with significantly better clinical outcomes compared to non-EE DES in patients suffering from T2DM. However, further research comparing EES with non-EE DES in insulin-treated and noninsulin-treated patients with T2DM are recommended.


ZD0473 combined with other chemotherapeutic agents for the treatment of solid malignancies.
Platinum-based combination chemotherapy regimens are the mainstay of current treatments for advanced solid malignancies. Preclinical in vitro studies have shown synergism with ZD0473 in combination with several agents, including vinorelbine and topotecan. This paper reviews the tolerability and activity observed with ZD0473 in combination with vinorelbine or topotecan, in two Phase I dose-escalating studies in patients with advanced, solid, refractory malignancies. Twenty-four patients were included in the ZD0473 plus vinorelbine trial and were treated with doses of ZD0473 60-150 mg/m2 and vinorelbine 15-25 mg/m2. In this trial, dose-limiting toxicity comprised non-haematological events and the most common grade 3/4 toxicities included neutropenia (54.2%), thrombocytopenia (29.2%) and anaemia (20.8%). Eleven patients were included in the ZD0473 plus topotecan trial and were treated with ZD0473 60-90 mg/m2 and topotecan 0.5 mg/m2/day for 3 or 5 days. In this trial, dose-limiting toxicity comprised haematological events and the most common grade 3/4 toxicities included thrombocytopenia (63.6%), neutropenia (36.4%) and anaemia (18.2%). No objective responses were observed in either trial, but disease stabilisation occurred in 29.2% and 27.3% of patients in the vinorelbine and topotecan trials, respectively.


Influence of fish oil on skeletal muscle mitochondrial energetics and lipid metabolites during high-fat diet.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) enhance insulin sensitivity and glucose homeostasis in rodent models of insulin resistance. These beneficial effects have been linked with anti-inflammatory properties, but emerging data suggest that the mechanisms may also converge on mitochondria. We evaluated the influence of dietary n-3 PUFAs on mitochondrial physiology and muscle lipid metabolites in the context of high-fat diet (HFD) in mice. Mice were fed control diets (10% fat), HFD (60% fat), or HFD with fish oil (HFD+FO, 3.4% kcal from n-3 PUFAs) for 10 wk. Body mass and fat mass increased similarly in HFD and HFD+FO, but n-3 PUFAs attenuated the glucose intolerance that developed with HFD and increased expression of genes that regulate glucose metabolism in skeletal muscle. Despite similar muscle triglyceride levels in HFD and HFD+FO, long-chain acyl-CoAs and ceramides were lower in the presence of fish oil. Mitochondrial abundance and oxidative capacity were similarly increased in HFD and HFD+FO compared with controls. Hydrogen peroxide production was similarly elevated in HFD and HFD+FO in isolated mitochondria but not in permeabilized muscle fibers, likely due to increased activity and expression of catalase. These results support a hypothesis that n-3 PUFAs protect glucose tolerance, in part by preventing the accumulation of bioactive lipid mediators that interfere with insulin action. Furthermore, the respiratory function of skeletal muscle mitochondria does not appear to be a major factor in sphingolipid accumulation, glucose intolerance, or the protective effects of n-3 PUFAs.


Differential suppression of vascular permeability and corneal angiogenesis by nonsteroidal anti-inflammatory drugs.
Angiogenesis, the formation of new capillary blood vessels, is an essential biological process under physiological conditions, including embryonic development, reproduction, and wound repair. Under pathologic conditions, this process plays a critical role in a variety of diseases such as cancer, rheumatoid arthritis, atherosclerosis, endometriosis, diabetic retinopathy, and age-related macular degeneration. The purpose of this study was to examine the effects of cyclooxygenase inhibitors on basic fibroblast growth factor (bFGF)- and vascular endothelial growth factor (VEGF)-mediated ocular neovascularization and permeability. A modified Miles vascular permeability assay was used to examine VEGF-induced vascular hyperpermeability, and the mouse corneal model of angiogenesis was used to compare the efficacy of systemic treatment with different nonsteroidal anti-inflammatory drugs (NSAIDs) on bFGF- and VEGF-induced angiogenesis. The authors demonstrated that systemic application of most NSAIDs, but not acetaminophen, blocked VEGF-induced permeability in mice. However, systemic treatment of mice with NSAIDs resulted in the differential inhibition of bFGF-induced (5%-57%) and VEGF-induced (3%-66%) corneal angiogenesis. The selective COX-2 inhibitors were more effective at suppressing bFGF-induced angiogenesis than VEGF-induced angiogenesis. Though most NSAIDS are effective at suppressing vascular leak, there exists a differential efficacy at suppressing the angiogenic response of specific cytokines such as bFGF and VEGF.


Antibiotic regimens for suspected early neonatal sepsis.
Early acquired infection may cause severe illness or death in the neonatal period. Prompt treatment with antibiotics has shown to reduce mortality. It is not clear which antibiotic regimen is suitable for treatment of presumed early neonatal sepsis. To compare effectiveness and adverse effects of antibiotic regimens for treatment of presumed early neonatal sepsis. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003), MEDLINE (1966 to August 2003), EMBASE (1980 to September 2003) and ZETOC (1993 to August 2003) databases were searched for possible studies. Pharmaceutical companies were contacted for any unpublished data. Randomised and quasi-randomised controlled studies comparing antibiotic regimens for the treatment of early neonatal sepsis (both monotherapies and combination therapies). Both reviewers screened abstracts and full reports against the inclusion criteria, appraised the quality of and extracted data from papers. For dichotomous outcomes, treatment effect was expressed as relative risk with 95% confidence interval. Meta-analysis was performed using a fixed effect model. Two small studies had compared monotherapy with combination therapy. There was no significant difference in mortality, treatment failure or bacteriological resistance. There is no evidence from randomised trials to suggest that any antibiotic regimen may be better than any other in the treatment of presumed early neonatal sepsis. More studies are needed to resolve this issue.


Near-germline human monoclonal antibodies neutralize and protect against multiple arthritogenic alphaviruses.
Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses that cause rheumatological disease in humans and include Chikungunya virus (CHIKV), Mayaro virus (MAYV), and others. Although serological evidence suggests that some antibody-mediated heterologous immunity may be afforded by alphavirus infection, the extent to which broadly neutralizing antibodies that protect against multiple arthritogenic alphaviruses are elicited during natural infection remains unknown. Here, we describe the isolation and characterization of MAYV-reactive alphavirus monoclonal antibodies (mAbs) from a CHIKV-convalescent donor. We characterized 33 human mAbs that cross-reacted with CHIKV and MAYV and engaged multiple epitopes on the E1 and E2 glycoproteins. We identified five mAbs that target distinct regions of the B domain of E2 and potently neutralize multiple alphaviruses with differential breadth of inhibition. These broadly neutralizing mAbs (bNAbs) contain few somatic mutations and inferred germline-revertants retained neutralizing capacity. Two bNAbs, DC2.M16 and DC2.M357, protected against both CHIKV- and MAYV-induced musculoskeletal disease in mice. These findings enhance our understanding of the cross-reactive and cross-protective antibody response to human alphavirus infections.


[Alternative treatments in cancer; extent and background of utilization].
To determine the prevalence of use of alternative cancer therapies, as well as the characteristics of the patients who use these therapies, and their experiences with them. Descriptive study. Outpatient departments of several hospitals in North-Holland. In total, 1091 patients were asked to participate in the study; 949 patients agreed (87%): 535 women (56%) and 414 men, with an average age of 62 years. The sample was stratified by diagnosis: 233 breast, 183 lung, 278 stomach/colon cancer and 255 patients with various other cancer diagnoses. A structured face-to-face interview and several written questionnaires were used. 2XOf the 949 patients, 9.4% were currently using an alternative therapy in addition to conventional treatment, and 5.8% had used an alternative treatment in the past but had subsequently stopped. Patients using alternative therapies were relatively younger and more highly educated than patients who chose not to use these therapies. Use of alternative therapies was more frequent among patients undergoing palliative treatment and patients who were actively dealing with the problems surrounding their disease. Only a minority of the patients believed they could be cured by the alternative therapy; the majority hoped it would help to slow the progression of their disease or strengthen their resistance. The motivation for seeking alternative treatment more often appears to be fear and uncertainty rather than belief in the efficacy of the treatment. For many patients the use of alternative therapies represents a means of dealing with the anxiety and stress surrounding their disease.


High sensitivity polymerase chain reaction assay for active and latent feline herpesvirus-1 infections in domestic cats.
A polymerase chain reaction (PCR) assay was developed and used to detect feline herpesvirus-1 (FHV-1) in conjunctival and oropharyngeal swabs, and in latently infected tissues (trigeminal ganglia, optic nerves, optic chiasma, olfactory bulbs and corneas) collected from 10 experimentally infected cats. There was good agreement between parallel tests of the swab specimens by PCR and virus isolation assay during the phase of acute, latent and recurrent disease episodes (kappa = 0.63, P < 0.001). The PCR reliably detected < or = 240 copies of FHV-1 template DNA, significantly improving upon previously published PCR assays for the agent.


Inflammatory molecules might become both biomarkers and therapeutic targets for stroke management.
Stroke is the fifth leading cause of death and the most frequent cause of disability worldwide. Currently, stroke diagnosis is based on neuroimaging; therefore, the lack of a rapid tool to diagnose stroke is still a major concern. In addition, therapeutic approaches to combat ischemic stroke are still scarce, since the only approved therapies are directed toward restoring blood flow to the affected brain area. However, due to the reduced time window during which these therapies are effective, few patients benefit from them; therefore, alternative treatments are urgently needed to reduce stroke brain damage in order to improve patients' outcome. The inflammatory response triggered after the ischemic event plays an important role in the progression of stroke; consequently, the study of inflammatory molecules in the acute phase of stroke has attracted increasing interest in recent decades. Here, we provide an overview of the inflammatory processes occurring during ischemic stroke, as well as the potential for these inflammatory molecules to become stroke biomarkers and the possibility that these candidates will become interesting neuroprotective therapeutic targets to be blocked or stimulated in order to modulate inflammation after stroke.


Exploring the microbial composition of Holstein Friesian and Belgian Blue colostrum in relation to the transfer of passive immunity.
For centuries, multicellular organisms have lived in symbiosis with microorganisms. The interaction with microorganisms has been shown to be very beneficial for humans and animals. During a natural birth, the initial inoculation with bacteria occurs when the neonate passes through the birth canal. Colostrum and milk intake are associated with the acquisition of a healthy gut flora. However, little is known about the microbial composition of bovine colostrum and the possible beneficial effects for the neonatal calf. In this prospective cohort study, the microbial composition of first-milking colostrum was analyzed in 62 Holstein Friesian (HF) and 46 Belgian Blue (BB) cows by performing amplicon sequencing of the bacterial V3-V4 region of the 16S rRNA gene. Calves received, 3 times, 2 L of their dam's colostrum within 24 h after birth. Associations between colostral microbial composition and its IgG concentration, as well as each calf's serum IgG levels, were analyzed. Colostrum samples were dominated by the phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. The 10 most abundant genera in the complete data set were Acinetobacter (16.2%), Pseudomonas (15.1%), a genus belonging to the Enterobacteriaceae family (4.9%), Lactococcus (4.0%), Chryseobacterium (3.9%), Staphylococcus (3.6%), Proteus (1.9%), Streptococcus (1.8%), Enterococcus (1.7%), and Enhydrobacter (1.5%). The remaining genera (other than these top 10) accounted for 36.5% of the counts, and another 8.7% were unidentified. Bacterial diversity differed significantly between HF and BB samples. Within each breed, several genera were found to be differentially abundant between colostrum of different quality. Moreover, in HF, the bacterial composition of colostrum leading to low serum IgG levels in the calf differed from that of colostrum leading to high serum IgG levels. Results of the present study indicate that the microbes present in colostrum are associated with transfer of passive immunity in neonatal calves.


The glucagon receptor antagonist LY2409021 has no effect on postprandial glucose in type 2 diabetes.
Type 2 diabetes (T2D) pathophysiology includes fasting and postprandial hyperglucagonemia, which has been linked to hyperglycemia via increased endogenous glucose production (EGP). We used a glucagon receptor antagonist (LY2409021) and stable isotope tracer infusions to investigate the consequences of hyperglucagonemia in T2D. A double-blinded, randomized, placebo-controlled crossover study was conducted. Ten patients with T2D and ten matched non-diabetic controls underwent two liquid mixed meal tests preceded by single-dose administration of LY2409021 (100 mg) or placebo. Double-tracer technique was used to quantify EGP. Antagonist selectivity toward related incretin receptors was determined in vitro. Compared to placebo, LY2409021 lowered the fasting plasma glucose (FPG) from 9.1 to 7.1 mmol/L in patients and from 5.6 to 5.0 mmol/L in controls (both P < 0.001) by mechanisms involving reduction of EGP. Postprandial plasma glucose excursions (baseline-subtracted area under the curve) were unaffected by LY2409021 in patients and increased in controls compared to placebo. Glucagon concentrations more than doubled during glucagon receptor antagonism. The antagonist interfered with both glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptors, complicating the interpretation of the postprandial data. LY2409021 lowered FPG concentrations but did not improve postprandial glucose tolerance after a meal in patients with T2D and controls. The metabolic consequences of postprandial hyperglucagonemia are difficult to evaluate using LY2409021 because of its antagonizing effects on the incretin receptors.


Is Anti-Müllerian Hormone Associated With Fecundability? Findings From the EAGeR Trial.
The objective of the study was to evaluate whether anti-Müllerian hormone (AMH) is associated with fecundability among women with proven fecundity and a history of pregnancy loss. This was a prospective cohort study within a multicenter, block-randomized, double-blind, placebo-controlled clinical trial ( clinicaltrials.gov , number NCT00467363). The study was conducted at four US medical centers (2006-2012). Participating women were aged 18-40 years, with a history of one to two pregnancy losses who were actively attempting pregnancy. Time to human chorionic gonadotropin detected and clinical pregnancy were assessed using Cox proportional hazard regression models to estimate fecundability odds ratios (fecundability odds ratios with 95% confidence interval [CI]) adjusted for age, race, body mass index, income, low-dose aspirin treatment, parity, number of previous losses, and time since most recent loss. Analyses examined by preconception AMH levels: low (<1.00 ng/mL, n = 124); normal (referent 1.00-3.5 ng/mL, n = 595); and high (>3.5 ng/mL, n = 483). Of the 1202 women with baseline AMH levels, 82 women with low AMH (66.1%) achieved an human chorionic gonadotropin detected pregnancy, compared with 383 with normal AMH (65.2%) and 315 with high AMH level (65.2%). Low or high AMH levels relative to normal AMH (referent) were not associated with fecundability (low AMH: fecundability odds ratios 1.13, 95% CI 0.85-1.49; high AMH: FOR 1.04, 95% CI 0.87-1.24). Lower and higher AMH values were not associated with fecundability in unassisted conceptions in a cohort of fecund women with a history of one or two prior losses. Our data do not support routine AMH testing for preconception counseling in young, fecund women.


Characterisation of CYP3A gene subfamily expression in human gastrointestinal tissues.
The human CYP3A subfamily is of interest due to its multiplicity, activity toward known carcinogens, and extrahepatic expression. In situ hybridisation analysis of formalin fixed, routinely processed biopsy specimens was used to localise CYP3A mRNA in human gastrointestinal tissues from several individuals. CYP3A mRNA is abundant in human liver and in mucosal epithelial cells of all segments of the human small intestine. RNA blot analyses showed that the mRNA species observed in most livers and in human small intestine represent CYP3A3/3A4 transcripts. This was confirmed at the protein level by immunoblot comparison of small intestine microsomes to in vitro expressed CYP3A4 and CYP3A5 proteins. In liver and small intestine, CYP3A mRNA is not uniformly distributed, with grain density highest in cells within the respective non-proliferative compartments. CYP3A mRNA was also observed in human oesophagus and colon. RNA blot analysis of multiple colons showed heterogeneity in the CYP3A mRNAs present. Two CYP3A mRNAs (CYP3A3/3A4 and CYP3A5) were detected in colon samples from several individuals. In addition to those localisation studies, the capacity of expressed CYP3A4 and CYP3A5 to activate the dietary heterocyclic amine MeIQ in the presence of alpha-naphthoflavone was shown. These results show that there is considerable heterogeneity in the expression of the CYP3A subfamily in human gastrointestinal tissues.


The content and composition of immunoreactive somatostatin in monkey pancreas.
A highly sensitive and specific radioimmunoassay (RIA) was developed for analyzing somatostatin (SRIF-LI). The monkey pancreas was lyophilized and extracted with 2N acetic acid. The content and composition of immunoreactive somatostatin in monkey pancreas were then evaluated by chromatography process and RIA. The concentration of SRIF-LI in monkey pancreas was around 513.8 ng/g dry weight. At least 3 components of SRIF-LI were detected in pancreatic extracts. The major component of SRIF-LI (about 92%) was SS-14, and other two were SS-28 and a form bigger than SS-28.


The changing epidemiology of invasive pneumococcal disease at a tertiary children's hospital through the 7-valent pneumococcal conjugate vaccine era: a case for continuous surveillance.
In 2000, a 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among US children. Many sites have since reported changes in invasive pneumococcal disease (IPD). We recognized an opportunity to describe the changes in epidemiology, clinical syndromes, and serotype distribution during a 14-year period including 4 years before vaccine introduction and spanning the entire PCV7 era. Cases were defined as children <18 years of age who were cared for at Primary Children's Medical Center for culture-confirmed IPD. We defined the prevaccine period as the time frame spanning from 1997 to 2000 and the postvaccine period from 2001 to 2010. Demographics, clinical data, and outcomes were collected through electronic query and chart review. Streptococcus pneumoniae serotyping was performed using the capsular swelling method. The median age of children with IPD increased from 19 months during the prevaccine period to 27 months during postvaccine period (P = 0.02), with a larger proportion of IPD among children older than 5 years. The proportion of IPD associated with pneumonia increased substantially from 29% to 50% (P < 0.001). This increase was primarily attributable to an increase in complicated pneumonia (17% to 33%, P < 0.001). Nonvaccine serotypes 7F, 19A, 22F, and 3 emerged as the dominant serotypes in the postvaccine period. In children with IPD who were younger than 5 years, for whom vaccine is recommended, 67% of the cases were caused by serotypes in 13-valent PCV during 2005 to 2010. After PCV7 was introduced, significant changes in IPD were noted. One-third of IPD occurred in children older than 5 years, who were outside the age-group for which PCV is recommended. Continued surveillance is warranted to identify further evolution of the epidemiology, clinical syndromes, and serotype distribution of S. pneumoniae after 13-valent PCV licensure.


Uncoupled forms of tyrosine hydroxylase unmask kinetic isotope effects on chemical steps.
Tyrosine hydroxylase (TyrH) catalyzes the hydroxylation of tyrosine to dihydroxyphenylalanine. In the proposed mechanism, a ferryl-oxo species attacks the aromatic ring of tyrosine, forming a cationic intermediate. However, no significant isotope effect is found for wild-type TyrH when 3,5-2H2-tyrosine is used as a substrate. The isotope effect has now been determined with 3,5-2H2-tyrosine using mutant forms of TyrH in which the oxidation of the pterin is uncoupled from hydroxylation of the amino acid. Three mutant enzymes exhibit significant inverse deuterium isotope effects and inverse solvent isotope effects. A proton inventory for the E326A enzyme is consistent with a normal solvent isotope effect of 2.4 on an unproductive step. The results support the proposed mechanism and demonstrate the utility of using mutant proteins with branched pathways to reveal isotope effects which are masked in the wild-type enzyme.


Improving diagnostic accuracy: Comparison of nomograms and classification tree analyses for predicting the diagnosis of oppositional defiant disorder.
Unstructured clinical interviews are inaccurate tools for diagnostic decision-making. While structured diagnostic evaluations improve reliability, they are infrequently used in clinical practice. Empirical approaches are a hallmark of evidenced-based assessment and may reduce burdens of structured interviews. We explore two approaches to empirical prediction of diagnosis, the naïve nomogram, and classification tree analysis (CTA). To illustrate the clinical utility of each approach, we compared their use in a sample of 6-year-olds (N = 619) to predict structured-interview diagnoses of oppositional defiant disorder (ODD). Findings indicate the accuracy of both approaches in predicting the absence of a disorder and improved detection of ODD using CTA for subgroups of children. Both empirical prediction techniques have applicability to diagnostic decision-making in psychiatry and pediatrics. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Superoscillation in speckle patterns.
Waves are superoscillatory where their local phase gradient exceeds the maximum wavenumber in their Fourier spectrum. We consider the superoscillatory area fraction of random optical speckle patterns. This follows from the joint probability density function of intensity and phase gradient for isotropic Gaussian random wave superpositions. Strikingly, this fraction is 1/3 when all the waves in the two-dimensional superposition have the same wavenumber. The fraction is 1/5 for a disk spectrum. Although these superoscillations are weak compared with optical fields with designed superoscillations, they are more stable on paraxial propagation.


Challenges in disaster data collection during recent disasters.
Gathering essential health data to provide rapid and effective medical relief to populations devastated by the effects of a disaster-producing event involves challenges. These challenges include response to environmental hazards, security of personnel and resources, political and economic issues, cultural barriers, and difficulties in communication, particularly between aid agencies. These barriers often impede the timely collection of key health data such as morbidity and mortality, rapid health and sheltering needs assessments, key infrastructure assessments, and nutritional needs assessments. Examples of these challenges following three recent events: (1) the Indian Ocean tsunami; (2) Hurricane Katrina; and (3) the 2010 earthquake in Haiti are reviewed. Some of the innovative and cutting-edge approaches for surmounting many of these challenges include: (1) the establishment of geographical information systems (GIS) mapping disaster databases; (2) establishing internet surveillance networks and data repositories; (3) utilization of personal digital assistant-based platforms for data collection; (4) involving key community stakeholders in the data collection process; (5) use of pre-established, local, collaborative networks to coordinate disaster efforts; and (6) exploring potential civil-military collaborative efforts. The application of these and other innovative techniques shows promise for surmounting formidable challenges to disaster data collection.


Treatment of homozygous familial hypercholesterolemia with low density lipoprotein apheresis: a 4 year follow-up study.
Hypercholesterolemia and elevated lipoprotein (a) (Lp[a]) levels are considered to be risk factors for the development and progression of premature atherosclerosis. The purpose of our report is to describe the effects of low density lipoprotein (LDL) apheresis (Liposorber system, Kanegafuchi Chemical Industrial Company LTD, Osaka, Japan) on serum lipoprotein concentrations and the clinical status in 2 male patients with homozygous familial hypercholesterolemia. Compared with pretreatment values, the posttreatment concentrations of total cholesterol, LDL cholesterol, and Lp(a) were significantly reduced by 50-60% (p < 0.0001). The concentration of high density lipoprotein (HDL) cholesterol was slightly affected. After one treatment session, LDL cholesterol and Lp(a) were decreased on average by 65% and then increased to reach about 70-75% of the pretreatment values before the next session. Prior to the treatment with LDL apheresis, each patient had suffered one myocardial infarction and had had 2 coronary angiographies. After treatment with LDL apheresis, neither cardiac complaints nor myocardial infarction were observed. The xanthomas were much decreased during the treatment or disappeared. We conclude that LDL apheresis can be continued safely and without major technical problems for several years. Apheresis effectively lowers the serum levels of total and LDL cholesterol. Furthermore, it reduces Lp(a), which is not influenced by lipid-lowering drugs. The reduction of LDL cholesterol and Lp(a) may delay the progression of the atherosclerotic process, thereby helping to reduce the risk of new episodes of coronary heart disease and thus extending the life expectancy in these patients.


Risk factors for 6-month continuation of S-1 adjuvant chemotherapy for gastric cancer.
The factors that affect the 6-month continuation of adjuvant chemotherapy with S-1 have not been fully evaluated. The objective of this retrospective study was to clarify the risk factors for 6-month continuation of S-1 adjuvant chemotherapy. The study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage 2 or 3 disease, had a serum creatinine level of ≤ 1.2 mg/dl, and received adjuvant S-1 between June 2002 and March 2011. One hundred of these patients were eligible for the present study. A comparison of 6-month continuation of S-1 stratified by various clinical factors, using the log-rank test, revealed a marginally significant difference in creatinine clearance (CCr) between those patients who continued for 6 months and those who did not. A CCr of 60 ml/min was regarded as the critical point. Uni- and multivariate Cox's proportional hazard analyses demonstrated that CCr was the only significant independent factor for the prediction of 6-month continuation. The 6-month continuation rate was 72.9 % in the patients with CCr ≥ 60 ml/min, and 40.0 % in patients with CCr <60 ml/min (P = 0.015). Adverse events occurred more frequently and earlier in the patients with CCr <60 ml/min than in those with CCr ≥ 60 ml/min. CCr <60 ml/min was a significant risk factor for 6-month continuation of S-1 adjuvant chemotherapy, even though the renal function was judged as normal by the serum creatinine level. Careful attention is therefore required for S-1 continuation in patients with CCr <60 ml/min.


Neuroretinal rim area in suspected glaucoma and early chronic open-angle glaucoma. Correlation with parameters of visual function.
The cup-disc ratio is an indirect measure of the amount of neural tissue present at the optic nerve head. A large cup-disc ratio in a large disc may be accompanied by a normal neuroretinal rim. The area of the neuroretinal rim is relatively constant in normal persons and should relate to visual function. In 39 eyes of patients with suspected glaucoma, normal subjects, and patients with early open-angle glaucoma, biometric findings, psychophysical functions, and optic nerve measurements were studied. The area of the neuroretinal rim was determined from stereophotographs and corrected for the magnification by the optical components of the eye. A statistically significant relation between this neuroretinal area and parameters of visual function was found. The cup-disc ratio correlated more weakly with visual function. Covariant analysis showed the neuroretinal area to be the only parameter capable in our sample of discriminating among the three clinical groups.


Multi-clade H5N1 virus-like particles: Immunogenicity and protection against H5N1 virus and effects of beta-propiolactone.
During the past decade, H5N1 highly pathogenic avian influenza (HPAI) viruses have diversified genetically and antigenically, suggesting the need for multiple H5N1 vaccines. However, preparation of multiple vaccines from live H5N1 HPAI viruses is difficult and economically not feasible representing a challenge for pandemic preparedness. Here we evaluated a novel multi-clade recombinant H5N1 virus-like particle (VLP) design, in which H5 hemagglutinins (HA) and N1 neuraminidase (NA) derived from four distinct clades of H5N1 virus were co-localized within the VLP structure. The multi-clade H5N1 VLPs were prepared by using a recombinant baculovirus expression system and evaluated for functional hemagglutination and neuraminidase enzyme activities, particle size and morphology, as well as for the presence of baculovirus in the purified VLP preparations. To remove residual baculovirus, VLP preparations were treated with beta-propiolactone (BPL). Immunogenicity and efficacy of multi-clade H5N1 VLPs were determined in an experimental ferret H5N1 HPAI challenge model, to ascertain the effect of BPL on immunogenicity and protective efficacy against lethal challenge. Although treatment with BPL reduced immunogenicity of VLPs, all vaccinated ferrets were protected from lethal challenge with influenza A/VietNam/1203/2004 (H5N1) HPAI virus, indicating that multi-clade VLP preparations treated with BPL represent a potential approach for pandemic preparedness vaccines.


Identification of four novel developmentally regulated gamma hemoglobin mRNA isoforms.
In the course of developing assays for the molecular prediction of biological age, we serendipitously discovered four novel isoforms of gamma hemoglobin mRNA, designated HBG1n1, HBG1n2, HBG2n2, and HBG2n3, collectively termed HBGn isoforms. Here we report the molecular characterization and tissue expression of these isoforms. RNA obtained from human peripheral blood and various fetal and adult tissues was amplified with duplex reverse transcription polymerase chain reaction (RT-PCR) assays to determine the expression profiles of the HBGn isoforms. To determine if their molecular origin was either a genomic recombination or an undefined RNA rearrangement event, DNA and RNA samples were pretreated with RNaseI and/or DNaseI and then analyzed with the duplex RT-PCR assays. Alignment analysis indicated that the HBG1n(1/2) and HBG2n(2/3) isoforms were identical to the expected parental HBG1 or HBG2 sequences except for unique deletions that spanned the 3' end of exon two, the entire second intron, and the 5' end of exon three. RT-PCR duplex reactions revealed that the isoforms exhibit restricted expression to fetal hematopoietic tissue and newborn peripheral blood and appear to be temporally regulated during development. Finally, nucleic acid digestion experiments illustrate that the isoforms appear to be created by an RNA rearrangement event between penta- or octanucleotide direct repeats in adjacent exons. The precise genesis and function of these novel isoforms is unknown at present. Interestingly, each of the four isoforms identified maintain an open reading frame as well as 5' and 3' regulatory regions invoking the possibility that they encode a family of related polypeptides.


Macroplastic pollution in freshwater environments: Focusing public and policy action.
Understanding and managing plastic pollution is an increasingly important environmental priority for policy makers, businesses and scientists. Awareness of the potential damage to the world's oceans has grown but there is less attention given to freshwater ecosystems. Yet, rivers are the dominant source of plastic pollution to the marine environment, as well as a potential sink, accumulating plastic from multiple sources. Actions to reduce the presence of macroplastics in rivers is fundamental to conserving both freshwater and marine environments, but there is limited understanding of potential pollution sources, vectors and storage. Importantly, there are only a handful of studies examining the typologies of freshwater macroplastic pollution, often using different categories and collection methods. This impedes setting priorities for scientific investigation and mitigation measures. The present study identifies the most prevalent macroplastic items in freshwater environments in Europe, with a focus on consumer plastic items, i.e. those that could potentially be reduced by targeted actions by the public, as well as industrial and government intervention. Our analysis addresses the differences between reported macroplastics in freshwater and marine environments as well as those estimated from litter rates. Our results identify a macroplastic "top ten", i.e. those dominant plastic typologies that require a more focused effort to reformulate their use and management, as well as setting a common baseline for a more consistent data gathering and reporting approach.


Negative effects of paternal age on children's neurocognitive outcomes can be explained by maternal education and number of siblings.
Recent findings suggest advanced paternal age may be associated with impaired child outcomes, in particular, neurocognitive skills. Such patterns are worrisome given relatively universal trends in advanced countries toward delayed nuptiality and fertility. But nature and nurture are both important for child outcomes, and it is important to control for both when drawing inferences about either pathway. We examined cross-sectional patterns in six developmental outcome measures among children in the U.S. Collaborative Perinatal Project (n = 31,346). Many of these outcomes at 8 mo, 4 y, and 7 y of age (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test) are negatively correlated with paternal age when important family characteristics such as maternal education and number of siblings are not included as covariates. But controlling for family characteristics in general and mother's education in particular renders the effect of paternal age statistically insignificant for most developmental measures. Assortative mating produces interesting relationships between maternal and paternal characteristics that can inject spurious correlation into observational studies via omitted variable bias. Controlling for both nature and nurture reveals little residual evidence of a link between child neurocognitive outcomes and paternal age in these data. Results suggest that benefits associated with the upward trend in maternal education may offset any negative effects of advancing paternal age.


A Proposal for Updated Standards of Photographic Documentation in Aesthetic Medicine.
In 1998, DiBernardo et al. published a very helpful standardization of comparative (before and after) photographic documentation. These standards prevail to this day. Although most of them are useful for objective documentation of aesthetic results, there are at least 3 reasons why an update is necessary at this time: First, DiBernardo et al. focused on the prevalent standards of medical photography at that time. From a modern perspective, these standards are antiquated and not always correct. Second, silver-based analog photography has mutated into digital photography. Digitalization offers virtually unlimited potential for image manipulation using a vast array of digital Apps and tools including, but not limited to, image editing software like Photoshop. Digitalization has given rise to new questions, particularly regarding appropriate use of editing techniques to maximize or increase objectivity. Third, we suggest changes to a very small number of their medical standards in the interest of obtaining a better or more objective documentation of aesthetic results. This article is structured into 3 sections and is intended as a new proposal for photographic and medical standards for the documentation of aesthetic interventions: 1. The photographic standards. 2. The medical standards. 3. Description of editing tools which should be used to increase objectivity.


Differences between the Health Assessment Questionnaire Disability Index (HAQ-DI) and the modified HAQ (mHAQ) score before and after infliximab treatment in patients with rheumatoid arthritis.
We conducted a 1-year prospective study to clarify differences between the Health Assessment Questionnaire disability index (HAQ-DI) and the modified HAQ (mHAQ) score among rheumatoid arthritis (RA) patients treated with infliximab. A total of 87 patients were scheduled to receive infliximab infusion at a dose of 3 mg/kg at weeks 0, 2, and 6, and every 8 weeks thereafter for 54 weeks; all patients received a full examination at each infusion appointment. The 28-joint disease activity score (DAS28) and functional capability of each patient was assessed at each visit, using the HAQ-DI and the mHAQ score. A strong correlation was observed between the HAQ-DI and the mHAQ score at baseline (r = 0.892). Over the course of the treatment, the mean mHAQ score changed similarly to the HAQ-DI, but the mean HAQ-DI was significantly higher than the mean mHAQ score at each time-point (for the HAQ-DI vs. mHAQ score, baseline: 1.5 +/- 0.7 vs. 0.9 +/- 0.6, p < 0.0001; 6 weeks: 1.1 +/- 0.7 vs. 0.6 +/- 0.5, p < 0.0001; 30 weeks: 1.0 +/- 0.7 vs. 0.6 +/- 0.5, p < 0.0001; 54 weeks: 0.9 +/- 0.7 vs. 0.6 +/- 0.6, p = 0.0006). In the categories of "eating", "reaching", and "other activities", the scores for several items excluded from the mHAQ score were significantly higher than those included in the mHAQ score over the year-long study period. We identified items contributing to significant differences between the HAQ-DI and the mHAQ score among RA patients treated with infliximab.


Megacystis secondary to myenteric plexus pathology. Presentation of two cases.
Herein, 2 cases of megacystis secondary to myenteric plexus pathology are reported. Unlike the entity of visceral myopathy, there was ganglion cell loss both in the bladder and in the colon of these 2 cases. Moreover, they did not present any gastrointestinal symptoms. Megacystis was the common pathology in these patients, whereas 1 of them suffered from unilateral vesicoureteral reflux. We could not find any similar report dealing with this phenomenon up to this time in the literature.


Home care nurses' experience of job stress and considerations for the work environment.
Home care nurses report increased stress in their jobs due to work environment characteristics that impact professional practice. Stressors and characteristics of the professional practice environment that moderate nurses' experience of job stress were examined in this embedded multiple case study. Real life experiences within a complex environment were drawn from interviews and observations with 29 participants across two home care agencies from one eastern U.S. state. Findings suggest that role overload, role conflict, and lack of control can be moderated in agencies where there are meaningful opportunities for shared decision making and the nurse-patient relationship is supported.


Controversies about fertility and pregnancy issues in young breast cancer patients: current state of the art.
For trying to help physicians in counseling their young patients with breast cancer interested in fertility preservation and future reproductive plans, this manuscript aims to perform an overview of the main available data on 10 controversies in this field. Thanks to the improvement in patients' prognosis, a growing attention towards fertility and pregnancy issues has been given over the past years and is currently provided to young breast cancer patients. However, several grey zones persist in many domains of this field and some physicians are still uncomfortable to deal with these issues. Despite the great number of breast cancer patients experiencing fertility and pregnancy concerns at the time of diagnosis, the pursuit of fertility preserving strategies is realized only for a small proportion of them. The lack of adequate oncofertility counseling at the time of anticancer treatment decisions and the high costs of fertility preserving procedures can be considered the main explanations for these findings. The several ongoing registries and prospective studies investigating fertility and pregnancy issues in young breast cancer patients are crucial to acquire more robust data and try to address and solve the still unmet controversies in this field.


Clearing of red blood cells in lumbar puncture does not rule out ruptured aneurysm in patients with suspected subarachnoid hemorrhage but negative head CT findings.
In evaluating the results of lumbar puncture (LP), a decrease in the number of red blood cells (RBCs)/mm3 between the first and fourth tubes collected (clearing) has often been assumed to indicate a traumatic puncture rather than the presence of subarachnoid hemorrhage (SAH). We tested the hypothesis that, in the setting of severe headache, CSF clearing coupled with an unremarkable unenhanced CT scan was negatively predictive of the presence of aneurysm and could be used to reduce the need for conventional arteriography. Cerebral angiography was performed to evaluate suspected SAH in 123 consecutive patients over 2 years at a university teaching hospital. Records of these patients were reviewed. Among the subset without SAH on CT scan, LP results were evaluated for clearing. Clearing was arbitrarily defined as a 25% reduction in RBCs between the first and fourth tubes. This subset's records were also reviewed for the presence of aneurysm at cerebral angiography or at follow-up 6 weeks later. Data were analyzed for correlation between clearing and aneurysm. Of the 123 patients whose records were reviewed, 22 did not show an SAH on CT scan. Of those 22 patients, eight had aneurysm at angiography and 14 did not. Clinical diagnoses in the other 14 included trauma, herpes meningitis, sickle cell disease, and cocaine use. CSF clearing was noted in 25% of those with an aneurysm (two of 8) and 21% of those without an aneurysm (three of 14). In the two cases with aneurysms, RBCs cleared from 3550 to 2550 (-28%) and from 24,686 to 17,842 (-28%), respectively. In the remaining six cases with aneurysms, RBCs increased a mean of 1370% between the first and fourth tubes (range, -22% to 7700%). Two of these six had a reduction that did not meet our criteria for clearing (-22% and -5.3%, respectively). In the 14 cases without aneurysms, RBCs increased a mean of 70% between the first and fourth tubes (range, -99% to 895%). In addition to the three of these 14 that met our criteria for clearing (-99%, -99%, and -43%), four cases had a reduction that did not (range, -0.7% to -14%). A 25% reduction in RBC concentration between the first and fourth tubes of CSF in patients with suspected SAH but negative CT findings occurs even in cases of ruptured aneurysms. Formal evaluation for the presence of an aneurysm is still necessary in this scenario.


Mitogen-activated protein kinase kinase kinase 4 deficiency in intrahepatic cholangiocarcinoma leads to invasive growth and epithelial-mesenchymal transition.
The molecular pathogenesis of intrahepatic cholangiocarcinoma (iCCA) is poorly understood, and its incidence continues to increase worldwide. Deficiency of mitogen-activated protein kinase kinase kinase 4 (MAP3K4) has been reported to induce the epithelial-mesenchymal transition (EMT) process of placental and embryonic development, yet its role in human cancer remains unknown. MAP3K4 has somatic mutation in iCCA so we sequenced all exons of MAP3K4 in 124 iCCA patients. We identified nine somatic mutations in 10 (8.06%) patients, especially in those with lymph node metastasis and intrahepatic metastasis. We also showed that messenger RNA and protein levels of MAP3K4 were significantly reduced in iCCA versus paired nontumor tissues. Furthermore, knockdown of MAP3K4 in cholangiocarcinoma cells markedly enhanced cell proliferation and invasiveness in vitro and tumor progression in vivo, accompanied by a typical EMT process. In contrast, overexpression of MAP3K4 in cholangiocarcinoma cells obviously reversed EMT and inhibited cell invasion. Mechanistically, MAP3K4 functioned as a negative regulator of EMT in iCCA by antagonizing the activity of the p38/nuclear factor κB/snail pathway. We found that the tumor-inhibitory effect of MAP3K4 was abolished by inactivating mutations. Clinically, a tissue microarray study containing 322 iCCA samples from patients revealed that low MAP3K4 expression in iCCA positively correlated with aggressive tumor characteristics, such as vascular invasion and intrahepatic or lymph node metastases, and was independently associated with poor survival and increased recurrence after curative surgery. MAP3K4, significantly down-regulated, frequently mutated, and potently regulating the EMT process in iCCA, was a putative tumor suppressor of iCCA.


Detection of impending reflex syncope by means of an integrated multisensor patch-type recorder.
We assessed the capability of an integrated multisensory patch-type monitor (RootiRx®) in detecting episodes of reflex (pre)syncope induced by tilt table test (TTT). Firstly, we performed an intrapatient comparison of cuffless systolic blood pressure (SBP), R-R interval (RRI) and variability (power spectrum analysis) obtained by means of the RootiRx® with those obtained with conventional methods (CONV) with validated finger pressure devices at baseline in supine position and repeatedly during TTT in 32 patients affected by likely reflex syncope. Secondly, the LF/HF values obtained with RootiRx® during TTT were analyzed in 50 syncope patients. Compared with baseline supine recordings, during TTT a decrement of median SBP was observed with CONV (-53.5 mmHg) but not with RootiRx® ®(-1 mmHg). Conversely, RRI reduction (CONV: 102 ms; RootiRx®: 127 ms) and RRI Low Frequency/High Frequency powers ratio (LF/HF) increase (CONV: 1.6; RootiRx®: 2.5) were similar. The concordance was good for RRI (0.97 [95% CI 0.96-0.98]) and fair for LF/HF ratio (0.69 [95% CI 0.46-0.83]). During the first 5 min of TTT the LF/HF ratio was higher in patients who later developed syncope than in no-syncope patients. This ratio was significantly different among patients with syncope, presyncope or without symptoms at the time of syncope (p value = 0.02). In conclusion, cuffless RootiRx® was unable to detect rapid drops of SBP occurring during impending reflex syncope and thus cannot be used as a diagnostic tool for hypotensive syncope. On the other hand, RRI mean values and LF/HF power ratios obtained with RootiRx® were consistent with those simultaneously obtained using conventional methods.


The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation.
Previous studies have shown that translation elongation is regulated by multiple factors, but the observed heterogeneity remains only partially explained. To dissect quantitatively the different determinants of elongation speed, we use probabilistic modeling to estimate initiation and local elongation rates from ribosome profiling data. This model-based approach allows us to quantify the extent of interference between ribosomes on the same transcript. We show that neither interference nor the distribution of slow codons is sufficient to explain the observed heterogeneity. Instead, we find that electrostatic interactions between the ribosomal exit tunnel and specific parts of the nascent polypeptide govern the elongation rate variation as the polypeptide makes its initial pass through the tunnel. Once the N-terminus has escaped the tunnel, the hydropathy of the nascent polypeptide within the ribosome plays a major role in modulating the speed. We show that our results are consistent with the biophysical properties of the tunnel.


Event-related desynchronization to contingent negative variation and self-paced movement paradigms in Parkinson's disease.
The event-related desynchronization (ERD) to voluntary movement is an indicator of cortical activation with a high time resolution and a specific spatial representation. We have evaluated 10 patients affected by Parkinson's disease (PD), free from L-dopa treatment for at least 12 hours, and 10 control subjects. Each subject underwent ERD examination during self-paced movement (SPM) and during contingent negative variation (CNV) paradigms. ERD was measured as the percentage decrease of alpha band power and calculated for frequency bands of 1 Hz, ranging between 8 and 12 Hz. For group comparisons, the frequency showing the highest ERD was selected for each subject and for each side. In the control group, ERD in the CNV paradigm began over the contralateral centroparietal electrodes 1475 ms before movement onset of the right hand and 1375 ms for the left. In the SPM paradigm, ERD started over the contralateral central electrodes 2150 ms and 1775 ms before movement onset of the right and left hand, respectively. In the PD group, ERD started over the contralateral central areas 800 ms and 475 ms before movement onset of the right and left hand, respectively, for CNV paradigm and 1200 ms and 750 ms for the right and left hand, respectively, for SPM paradigm. Therefore, contralateral ERD began closer to movement onset in PD compared with the control group in both paradigms. ERD over the sensorimotor areas ipsilateral to the movement was not significantly different in PD compared with the control group. The finding of delayed contralateral ERD in PD is according to the view that functional cortical activation related to movement preparation is impaired in PD. The lack of group differences in the onset of ipsilateral ERD, which appears close to movement execution than contralateral ERD both in normal subjects and in PD, suggests that different mechanisms may be involved in generating ERD over the hemispheres ipsilateral and contralateral to the movement, and that only the latter are impaired in PD.


Pertussis immunisation and serious acute neurological illnesses in children.
To determine long term outcome in children who had a severe acute neurological illness in early childhood associated with pertussis immunisation. Follow up study of cases and matched controls. Assessment of children at home and at school throughout Britain. Children recruited into the national childhood encephalopathy study in 1976-9 were followed up, with one of their two original matched controls, in 1986-9. Performance in educational attainment tests; behaviour problems reported by teachers and parents; continuing convulsions; evidence of other neurological or physical dysfunction. Over 80% of cases and controls were traced. Case children were significantly more likely than controls to have died or to have some form of educational, behavioural, neurological, or physical dysfunction a decade after their illness. The prevalence of one or more of these adverse outcomes in case children who had been immunised with diphtheria, tetanus, and pertussis vaccine within seven days before onset of their original illness was similar to that in case children who had not been immunised recently. The relative risk for recent diphtheria, tetanus, and pertussis immunisation in children who had died or had any dysfunction in comparison with controls was 5.5 (95% confidence interval 1.6 to 23.7). However, the number of cases associated with vaccine (12) was extremely small and statistically vulnerable, and other possible agents or predisposing factors could not be excluded. Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated with the development of severe acute neurological illnesses that can have serious sequelae. Some cases may occur by chance or have other causes. The role of pertussis vaccine as a prime or concomitant factor in the aetiology of these illnesses cannot be determined in any individual case. The balance of possible risk against known benefits from pertussis immunisation supports continued use of the vaccine.


[Variation of the parasite density of Plasmodium falciparum in asymptomatic carriers: consequences for malaria chemoresistance studies].
During the studies on malaria chemoresistance, we noted great variations in parasite density of Plasmodium falciparum between screening in the morning and final selection in the afternoon, in asymptomatic people. To better understand this phenomenon, we conducted a study in october 1987 on primary school children in a village near the city of Bobo-Dioulasso, at the peak malaria prevalence. We performed 3 blood-smears at 8 a.m., 2 p.m. and 8 p.m., on Day 0 and Day 4, to an initial number of 86 children, aged from 6 to 9 years. By the end of the study 44 children remained who fulfilled the inclusion criteria Among them 35 showed a parasitaemia on Day 0 and 9 remained negative. On Day 4, 28 were positive and 16 remained negative. Of the 35 children positive at entry to the study 16 remained continuously positive, the others were negative on at least one occasion. Of the 28 children positive on Day 4, 14 remained continuously positive. For the 16 people with a parasitaemia continuously positive on Day 0.7 (43.7 p. cent) became spontaneously negative on Day 4. But considering the small size of our sample, the analysis of the nycthemeral variation and of the variation between the two days did not show a significant difference. Further studies involving a greater number of blood-smears during a longer period and concerning more people, should be conducted. The possibility of spontaneous negativation of the parasitaemia without drug absorption shows that there are some cases of false malaria chemosensitivity that are declared when the in vivo tests are not coupled with in vitro tests.


Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein.
Circular RNAs (circRNAs) have been proven to function as competing endogenous RNAs to interact with microRNAs (miRNAs) and influence the expression of miRNA target mRNAs. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of intervertebral disc degeneration (IVDD). The role and mechanism of a circRNA, circVMA21, in IVDD were explored in nucleus pulposus (NP) cells and degenerative NP tissues from patients and rat models. The interaction between circVMA21 and miR-200c as well as the target mRNA, X linked inhibitor-of-apoptosis protein (XIAP), was examined. The decreased expression of XIAP in the inflammatory cytokines-treated NP cells and the degenerative NP tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix. miR-200c regulated NP cell viability and functions through inhibiting XIAP. circVMA21 acted as a sponge of miR-200c and functioned in NP cells through targeting miR-200c and XIAP. Intradiscal injection of circVMA21 alleviated IVDD in the rat model. CircVMA21 could alleviate inflammatory cytokines-induced NP cell apoptosis and imbalance between anabolism and catabolism of extracellular matrix through miR-200c-XIAP pathway. It provides a potentially effective therapeutic strategy for IVDD.


EPOC Comparison Between Resistance Training and High-Intensity Interval Training in Aerobically Fit Women.
Previous research has shown that various modes of exercise may elicit significant increases in resting metabolism for up to 24 hours post-exercise, but typically using untrained or moderately active subjects. The purpose of the present study was to compare excess post-exercise oxygen consumption (EPOC) between circuit-style resistance training (RT) and high-intensity interval training (HIIT) in young, aerobically fit women. During the follicular phase of the menstrual cycle, seven participants reported to the laboratory for evening and morning baseline resting metabolic rate (RMR) measurements via indirect calorimetry. Participants fasted and slept overnight in the laboratory between RMR measurements. Following the morning RMR measurement, participants were randomly assigned to complete either a total-body, circuit-style RT protocol (30 seconds of lifting at 80% 1RM:one minute rest) or treadmill HIIT (30-second run at 90% VO2 max:one minute stationary recovery). RMR was repeated 14 and 24 hours post-exercise. All procedures were replicated during the follicular phase of the next menstrual cycle using the remaining exercise protocol. Resting VO2 was significantly (p<0.05) higher 14 hours after RT (3.8±0.3 ml/kg/min) compared to baseline (3.4±0.3 ml/kg/min), however HIIT showed no significant change (3.7±0.3 ml/kg/min). Both RT and HIIT showed significantly higher energy expenditure 14 hours post-exercise (33±5 and 33±4 kcals/30 minutes, respectively) compared to baseline (30±3 kcal). Neither protocol sustained a RMR change at 24 hours. Based on the magnitude and duration of post-exercise energy expenditure, EPOC responses may be a worthwhile consideration when prescribing exercise for weight maintenance in young, fit women.


Voluntary self-initiation of the stimuli onset improves working memory and accelerates visual and attentional processing.
The ability of an organism to voluntarily control the stimuli onset modulates perceptual and attentional functions. Since stimulus encoding is an essential component of working memory (WM), we conjectured that controlling the initiation of the perceptual process would positively modulate WM. To corroborate this proposition, we tested twenty-five healthy subjects in a modified-Sternberg WM task under three stimuli presentation conditions: an automatic presentation of the stimuli, a self-initiated presentation of the stimuli (through a button press), and a self-initiated presentation with random-delay stimuli onset. Concurrently, we recorded the subjects' electroencephalographic signals during WM encoding. We found that the self-initiated condition was associated with better WM accuracy, and earlier latencies of N1, P2 and P3 evoked potential components representing visual, attentional and mental review of the stimuli processes, respectively. Our work demonstrates that self-initiated stimuli enhance WM performance and accelerate early visual and attentional processes deployed during WM encoding. We also found that self-initiated stimuli correlate with an increased attentional state compared to the other two conditions, suggesting a role for temporal stimuli predictability. Our study remarks on the relevance of self-control of the stimuli onset in sensory, attentional and memory updating processing for WM.


[Process management in a radiology department. Impact on the quality system].
The purpose of this work was the transition from a mode of management combining TQM (Total Quality Management) based on the European model "EFQM", and quality assurance based on the ISO 9001-1994 certification model, to the ISO 9001-2000 certification model which imposes process management and integrates both management and quality assurance. In order to visualize the inter-relation between processes, a processes-map was made. That is to say a representation of the organization in terms of inputs and outputs. Those processes were divided step by step, from general to final processes which were translated into an algorithmic approach. Subsequently, two external auditors were asked to evaluate the new quality system. They used three quality standards (IOS 9001-2000, MFQ and ANAES) in order to determine the adaptation score of the quality system. Finally, the implementation of the department documentation system on an intranet was evaluated by means of two questionnaires: a qualitative one, dealing with staff acceptability, and a quantitative one, dealing with research effectiveness.


Magical attachment: Children in magical relations with hospital clowns.
The aim of the present study was to achieve a theoretical understanding of several different-age children's experiences of magic relations with hospital clowns in the context of medical care, and to do so using psychological theory and a child perspective. The method used was qualitative and focused on nine children. The results showed that age was important to consider in better understanding how the children experienced the relation with the hospital clowns, how they described the magical aspects of the encounter and how they viewed the importance of clown encounters to their own well-being. The present theoretical interpretation characterized the encounter with hospital clowns as a magical safe area, an intermediate area between fantasy and reality. The discussion presented a line of reasoning concerning a magical attachment between the child and the hospital clowns, stating that this attachment: a) comprised a temporary relation; b) gave anonymity; c) entailed reversed roles; and d) created an emotional experience of boundary-transcending opportunities.


Theoretical and experimental studies of the reactions between hyperthermal O(3P) and graphite: graphene-based direct dynamics and beam-surface scattering approaches.
Beam-surface scattering experiments and theoretical direct dynamics based on density functional theory calculations are used to investigate hyperthermal collisions between O((3)P) and highly oriented pyrolytic graphite (HOPG). The simulations suggest that the HOPG surface becomes functionalized with epoxide groups. Intersystem crossing (ISC) between the lowest-energy triplet and singlet potential-energy surfaces is not necessary for this functionalization to occur. Both theory and experiment indicate that incoming O atoms can react at the surface to form O(2) by way of an Eley-Rideal mechanism. They also suggest that the collisions can result in the production of CO and CO(2) by way of both direct and complex reaction mechanisms. The direct dynamics simulations provide significant insight into the details of the complex reaction mechanisms. Semiquinones are present at defect sites and can form in functionalized pristine sheets, the latter resulting in the formation of a defect. Direct collision of an incoming O atom with a semiquinone or vibrational excitation caused by a nearby O-atom collision can cause the release of the semiquinone CO, forming carbon monoxide. The CO may react with an oxygen atom on the surface to become CO(2) before receding from the surface. The simulations also illustrate how epoxide groups neighboring semiquinones catalyze the release of CO. Throughout, the experimental results are observed to be consistent with the theoretical calculations.


Facilitating engagement of persons with opioid use disorder in treatment for hepatitis C virus infection via telemedicine: Stories of onsite case managers.
Although hepatitis C virus (HCV) infection has high prevalence and incidence in persons with opioid use disorder (PWOUD), their engagement in HCV care has been limited due to a variety of factors. In an ongoing multisite study at 12 opioid treatment programs (OTPs) throughout New York State (NYS), we have been evaluating telemedicine accompanied by onsite administration of direct acting antiviral (DAA) medications compared with usual care including offsite referral to a liver specialist for HCV management. Each site has a case manager (CM) who is responsible for all study-related activities including participant recruitment, facilitating telemedicine interactions, retention in care, and data collection. Our overall objective is to analyze CM experiences of clients' stories and events to understand how the telemedicine model facilitates HCV treatment. Hermeneutic phenomenology was used to interpret and to explicate common meanings and shared practices of the phenomena of case management, and a focus group with CMs was conducted to reinforce and expand on key themes identified from the CMs' stories. We identified three themes: (1) building trust, (2) identification of multiple competing priorities, and (3) development of personalized care approaches. Our results illustrate that trust is a fundamental pillar on which the telemedicine system can be based. Participants' experiences at the OTP can reinforce trust. Understanding the specific competing priorities and routinizing dedicated personalized approaches to overcome them are key to increasing participation in HCV care among PWOUD.


Removal of cytostatic drugs from aquatic environment: a review.
Cytostatic drugs have been widely used for chemotherapy for decades. However, many of them have been categorized as carcinogenic, mutagenic and teratogenic compounds, triggering widespread concerns about their occupational exposure and ecotoxicological risks to the environment. This review focuses on trace presence, fate and ecotoxicity of various cytostatic compounds in the environment, with an emphasis on the major sources contributing to their environmental concentrations. Past records have documented findings mainly on hospital effluents though little effort has been directed to household discharges. There is also a lack in physico-chemical data for forecasting the chemodynamics of cytostatics in natural waters along with its human metabolites and environmental transformation products. In this light, obtaining comprehensive ecotoxicity data is becoming pressingly crucial to determine their actual impacts on the ecosystem. Literature review also reveals urinary excretion as a major contributor to various cytostatic residues appeared in the water cycle. As such, engaging urine source-separation as a part of control strategy holds a rosy prospect of addressing the "emerging" contamination issue. State-of-the-art treatment technologies should be incorporated to further remove cytostatic residues from the source-separating urine stream. The benefits, limitations and trends of development in this domain are covered for membrane bio-reactor, reverse/forward osmosis and advanced oxidation processes. Despite the respective seeming advantages of source separation and treatment technology, a combined strategy may cost-effectively prevent the cytostatic residues from seeping into the environment. However, the combination calls for further evaluation on the associated technological, social-economic and administrative issues at hand.


Disrupting reconsolidation of fear memory in humans by a noradrenergic β-blocker.
The basic design used in our human fear-conditioning studies on disrupting reconsolidation includes testing over different phases across three consecutive days. On day 1 - the fear acquisition phase, healthy participants are exposed to a series of picture presentations. One picture stimulus (CS1+) is repeatedly paired with an aversive electric stimulus (US), resulting in the acquisition of a fear association, whereas another picture stimulus (CS2-) is never followed by an US. On day 2 - the memory reactivation phase, the participants are re-exposed to the conditioned stimulus without the US (CS1-), which typically triggers a conditioned fear response. After the memory reactivation we administer an oral dose of 40 mg of propranolol HCl, a β-adrenergic receptor antagonist that indirectly targets the protein synthesis required for reconsolidation by inhibiting the noradrenaline-stimulated CREB phosphorylation. On day 3 - the test phase, the participants are again exposed to the unreinforced conditioned stimuli (CS1- and CS2-) in order to measure the fear-reducing effect of the manipulation. This retention test is followed by an extinction procedure and the presentation of situational triggers to test for the return of fear. Potentiation of the eye blink startle reflex is measured as an index for conditioned fear responding. Declarative knowledge of the fear association is measured through online US expectancy ratings during each CS presentation. In contrast to extinction learning, disrupting reconsolidation targets the original fear memory thereby preventing the return of fear. Although the clinical applications are still in their infancy, disrupting reconsolidation of fear memory seems to be a promising new technique with the prospect to persistently dampen the expression of fear memory in patients suffering from anxiety disorders and other psychiatric disorders.


Nosocomial infections: a glimpse into the '80s.
The 1970s saw many changes in the way physicians dealt with infections. For example, greater emphasis was placed on specific risk environments rather than on the hospital's general physical environment and significant progress was made in controlling diseases such as post-transfusion hepatitis. Many challenges remain for the '80s, however, such as development of a data base to determine what infection control practices are the most cost-effective and development of a model for describing and measuring infection risk.


Neonatal clomipramine treatment in the rat does not affect social, sexual and exploratory behaviors in adulthood.
The potential ability of the tricyclic anti-depressant clomipramine to cause an increase in anxiety in adult animals following neonatal treatment with the drug has been investigated; no such anxiogenic actions were found in the social interaction test. Furthermore, the behavior of animals that had received the drug as pups did not differ from that of the controls in open field or holeboard tests, nor in tests of sexual behavior, aggressive and dominance behaviors or passive avoidance learning.


Recognition of homeology by the wheat Ph1 locus.
Chromosome 1A(m) of Triticum monococcum is closely homeologous to T. aestivum chromosome 1A but recombines with it little in the presence of the wheat suppressor of homeologous chromosome pairing, Ph1. In the absence of Ph1, the two chromosomes recombine as if they were completely homologous. Chromosomes having either terminal or interstitial segments of chromosome 1A(m) in 1A were constructed and their recombination with 1A was investigated in the presence of Ph1. No recombination was detected in the homeologous (1A(m)/1A) segments, irrespective of whether terminally or interstitially positioned in a chromosome, whereas the levels of recombination in the juxtaposed homologous (1A/1A) segments was normal or close to normal relative to completely homologous 1A chromosomes. These observations show that Phl does not regulate chromosome pairing by premeiotic chromosome alignment and a mitotic spindle-centromere interaction, as has been suggested, but processes homology along the entire length of chromosomes.


Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism.
In recent years, the central nervous system (CNS) has emerged as a principal site of insulin action. This notion is supported by studies in animals relying on intracerebroventricular insulin infusion and by experiments in humans that make use of the intranasal pathway of insulin administration to the brain. Employing neurobehavioural and metabolic measurements as well as functional imaging techniques, these studies have provided insight into a broad range of central and peripheral effects of brain insulin. The present review focuses on CNS effects of insulin administered via the intranasal route on cognition, in particular memory function, and whole-body energy homeostasis including glucose metabolism. Furthermore, evidence is reviewed that suggests a pathophysiological role of impaired brain insulin signaling in obesity and type 2 diabetes, which are hallmarked by peripheral and possibly central nervous insulin resistance, as well as in conditions such as Alzheimer's disease where CNS insulin resistance might contribute to cognitive dysfunction.


Preparation and characterization of porous apatite ceramics coated with beta-tricalcium phosphate.
Hydroxyapatite (Ca10(PO4)6(OH)2; HA) is one of the most biocompatible materials with bones, and porous HA is promising bone substitute materials for clinical applications. While there are reports that beta-tricalcium phosphate (Ca3(PO4)2; TCP) has higher resorbability than HA when the material is implanted in a bone defect. In the present study, porous HA coated with beta-TCP was prepared by our unique method. The porous HA of about 60% porosity with interconnecting pore structure was soaked in diammonium hydrogen phosphate solution, and then the HA was sintered at 900 degrees C for 3 h. beta-TCP was revealed by X-ray diffractometry on the surface of porous HA. It was possible to control the content of surface-formed beta-TCP arbitrary by varying the concentration of the solution. The obtained HA coated with 33 wt% beta-TCP (33TCP) had about 60% open porosity with the pore size from 150 to 400 microns. The average compressive strength of this porous ceramics was 17.5 MPa. Surface coated HA with beta-TCP deprived of the brittleness in handling. The weight of HA implanted into muscles was increased obviously at 4 weeks because of formation of carbonate hydroxyapatite on the surface of HA. The weight of 33TCP was scarcely changed up to 12 weeks, but the weight tended to increase at 24 weeks. The carbonate hydroxyapatite was not formed on 33TCP at 4 weeks, but formed on it at 24 weeks. Therefore beta-TCP coated porous HA behaved like beta-TCP initially after implantation, and then behaved like HA.


A self-compartmentalizing hexamer serine protease from Pyrococcus horikoshii: substrate selection achieved through multimerization.
Oligopeptidases impose a size limitation on their substrates, the mechanism of which has long been under debate. Here we present the structure of a hexameric serine protease, an oligopeptidase from Pyrococcus horikoshii (PhAAP), revealing a complex, self-compartmentalized inner space, where substrates may access the monomer active sites passing through a double-gated "check-in" system, first passing through a pore on the hexamer surface and then turning to enter through an even smaller opening at the monomers' domain interface. This substrate screening strategy is unique within the family. We found that among oligopeptidases, a residue of the catalytic apparatus is positioned near an amylogenic β-edge, which needs to be protected to prevent aggregation, and we found that different oligopeptidases use different strategies to achieve such an end. We propose that self-assembly within the family results in characteristically different substrate selection mechanisms coupled to different multimerization states.


Adolescent alcohol, nuts, and fiber: combined effects on benign breast disease risk in young women.
Adolescent drinking is associated with higher risks of proliferative benign breast disease (BBD) and invasive breast cancer (BC). Furthermore, adolescent nut and fiber consumptions are associated with lower risks of benign lesions and premenopausal BC. We hypothesize that diet (nuts, fiber) may mitigate the elevated BBD risk associated with alcohol. A prospective cohort of 9031 females, 9-15 years at baseline, completed questionnaires in 1996-2001, 2003, 2005, 2007, 2010, 2013, and 2014. Participants completed food frequency questionnaires in 1996-2001. In 2005, participants (>=18 years) began reporting biopsy-confirmed BBD (N = 173 cases). Multivariable logistic regression estimated associations between BBD and cross-classified intakes (14-17 years) of alcohol and peanut butter/nuts (separately, total dietary fiber). Only 19% of participants drank in high school; drinking was associated with elevated BBD risk (OR = 1.75, 95% CI: 1.20-2.56; p = 0.004) compared to nondrinkers. Participants consuming any nuts/butter had lower BBD risk (OR = 0.64, 95% CI: 0.45-0.90; p = 0.01) compared to those consuming none. Participants in top 75% fiber intake had lower risk (OR = 0.57, 95% CI: 0.40-0.81; p = 0.002) compared to bottom quartile. Testing our hypothesis that consuming nuts/butter mitigates the elevated alcohol risk, analyzing alcohol and nuts combined found that those who consumed both had lower risk (RR = 0.47, 95% CI: 0.24-0.89; p = 0.02) compared to drinkers eating no nuts. Our analysis of alcohol and fiber together did not demonstrate risk mitigation by fiber. For high school females who drink, their BBD risk may be attenuated by consuming nuts. Due to modest numbers, future studies need to replicate our findings in adolescent/adult females. However, high school students may be encouraged to eat nuts and fiber, and to avoid alcohol, to reduce risk of BBD and for general health benefits.


Unusual presentation of obscure Meckel diverticulum treated with robot-assisted diverticulectomy: A case report.
Meckel diverticulum (MD) is the most common congenital abnormality of gastrointestinal tract. Tough believed to occur in 2% of population, most of them remain veiled because majority are clinically asymptomatic and remain obscure in radiological examination. A 26-year-old male with episodic black colored stool since last 10 years. Tough symptomatic, diagnosis of pathological lesion, and the bleeding site could not be established with any of the sophisticated diagnostic technique. After 10 years, it was finally diagnosed as MD with careful observation of bowel loops on computed tomography enterography (CTE) where remnant of vitelline vessel and hyper-enhancing nodule are seen along the wall of diverticular loop. The patient underwent robot assisted laparoscopic surgery with excision of diverticular loop. To the best of our knowledge, this robot-assistant Meckel diverculectomy is probably the first reported surgical procedure in PubMed. Follow-up for 3 month showed no complication or recurrence. Every case is unique and we must be aware and remain alert in tracing the possible morphological variation of the case. Here, we present one unique but rare feature of MD, which helped us in making diagnosis.


Profiling post-COVID-19 condition across different variants of SARS-CoV-2: a prospective longitudinal study in unvaccinated wild-type, unvaccinated alpha-variant, and vaccinated delta-variant populations.
Self-reported symptom studies rapidly increased understanding of SARS-CoV-2 during the COVID-19 pandemic and enabled monitoring of long-term effects of COVID-19 outside hospital settings. Post-COVID-19 condition presents as heterogeneous profiles, which need characterisation to enable personalised patient care. We aimed to describe post-COVID-19 condition profiles by viral variant and vaccination status. In this prospective longitudinal cohort study, we analysed data from UK-based adults (aged 18-100 years) who regularly provided health reports via the Covid Symptom Study smartphone app between March 24, 2020, and Dec 8, 2021. We included participants who reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2 who subsequently developed long COVID (ie, symptoms lasting longer than 28 days from the date of the initial positive test). We separately defined post-COVID-19 condition as symptoms that persisted for at least 84 days after the initial positive test. We did unsupervised clustering analysis of time-series data to identify distinct symptom profiles for vaccinated and unvaccinated people with post-COVID-19 condition after infection with the wild-type, alpha (B.1.1.7), or delta (B.1.617.2 and AY.x) variants of SARS-CoV-2. Clusters were then characterised on the basis of symptom prevalence, duration, demography, and previous comorbidities. We also used an additional testing sample with additional data from the Covid Symptom Study Biobank (collected between October, 2020, and April, 2021) to investigate the effects of the identified symptom clusters of post-COVID-19 condition on the lives of affected people. We included 9804 people from the COVID Symptom Study with long COVID, 1513 (15%) of whom developed post-COVID-19 condition. Sample sizes were sufficient only for analyses of the unvaccinated wild-type, unvaccinated alpha variant, and vaccinated delta variant groups. We identified distinct profiles of symptoms for post-COVID-19 condition within and across variants: four endotypes were identified for infections due to the wild-type variant (in unvaccinated people), seven for the alpha variant (in unvaccinated people), and five for the delta variant (in vaccinated people). Across all variants, we identified a cardiorespiratory cluster of symptoms, a central neurological cluster, and a multi-organ systemic inflammatory cluster. These three main clusers were confirmed in a testing sample. Gastrointestinal symptoms clustered in no more than two specific phenotypes per viral variant. Our unsupervised analysis identified different profiles of post-COVID-19 condition, characterised by differing symptom combinations, durations, and functional outcomes. Our classification could be useful for understanding the distinct mechanisms of post-COVID-19 condition, as well as for identification of subgroups of individuals who might be at risk of prolonged debilitation. UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, UK Alzheimer's Society, and ZOE.


Role of transport performance for neuron cell morphology.
The compartmental model is a basic tool for studying signal propagation in neurons; if the model parameters are adequately redefined, it can also be helpful in the study of electrical or fluid transport in other biological systems. Here we show that the input resistance in different networks that simulate the morphology of neurons is the result of the interplay between the relevant conductances, neuron morphology, and neuron size. The results suggest that neurons may grow in such a way that facilitates the current flow to the synapses, concurrently minimizing power consumption.


Evaluation of membrane oxygenators and reservoirs in terms of capturing gaseous microemboli and pressure drops.
An increasing amount of evidence points to cerebral embolization during cardiopulmonary bypass (CPB) as the principal etiologic factor of neurologic complications. In this study, the capability of capturing and classification of gaseous emboli and pressure drop of three different membrane oxygenators (Sorin Apex, Terumo Capiox SX25, Maquet QUADROX) were measured in a simulated adult model of CPB using a novel ultrasound detection and classification quantifier system. The circuit was primed with 1000 mL heparinized human packed red blood cells and 1000 mL lactated Ringer's solution (total volume 2000 mL, corrected hematocrit 26-28%). After the injection of 5 mL air into the venous line, an Emboli Detection and Classification Quantifier was used to simultaneously record microemboli counts at post-pump, post-oxygenator, and post-arterial filter sites. Trials were conducted at normothermic (35 degrees C) and hypothermic (25 degrees C) conditions. Pre-oxygenator and post-oxygenator pressure were recorded in real time and pressure drop was calculated. Maquet QUADROX membrane oxygenator has the lowest pressure drops compared to the other two oxygenators (P < 0.001). The comparison among the three oxygenators indicated better capability of capturing gaseous emboli with the Maquet QUADROX and Terumo Capiox SX25 membrane oxygenator and more emboli may pass through the Sorin Apex membrane oxygenator. Microemboli counts uniformly increased with hypothermic perfusion (25 degrees C). Different types of oxygenators and reservoirs have different capability of capturing gaseous emboli and transmembrane pressure drop. Based on this investigation, Maquet QUADROX membrane oxygenator has the lowest pressure drop and better capability for capturing gaseous microemboli.


[Hygienic assessment of innovation procedures for lesson scheduling at school].
Hygienic assessment has established that education, by using innovation procedures for school lesson scheduling, diminishes the weariness of a schooling load and optimizes the pupils' psychosomatic status and school routine.


Activation of neurons in the hypothalamic dorsomedial nucleus via hypothalamic projections of the nucleus of the solitary tract following refeeding of fasted rats.
We report that satiation evokes neuronal activity in the ventral subdivision of the hypothalamic dorsomedial nucleus (DMH) as indicated by increased c-fos expression in response to refeeding in fasted rats. The absence of significant Fos activation following food presentation without consumption suggests that satiation but not craving for food elicits the activation of ventral DMH neurons. The distribution pattern of the prolactin-releasing peptide (PrRP)-immunoreactive (ir) network showed remarkable correlations with the distribution of activated neurons within the DMH. The PrRP-ir fibers and terminals were immunolabeled with tyrosine hydroxylase, suggesting their origin in lower brainstem instead of local, hypothalamic PrRP cells. PrRP-ir fibers arising from neurons of the nucleus of the solitary tract could be followed to the hypothalamus. Unilateral transections of these fibers at pontine and caudal hypothalamic levels resulted in a disappearance of the dense PrRP-ir network in the ventral DMH while PrRP immunoreactivity was increased in transected fibers caudal to the knife cuts as well as in perikarya of the nucleus of the solitary tract ipsilateral to the transections. In accord with these changes, the number of Fos-expressing neurons following refeeding declined in the ipsilateral but remained high in the contralateral DMH. However, the Fos response in the ventral DMH was not attenuated following chemical lesion (neonatal monosodium glutamate treatment) of the hypothalamic arcuate nucleus, another possible source of DMH inputs. These findings suggest that PrRP projections from the nucleus of the solitary tract contribute to the activation of ventral DMH neurons during refeeding, possibly by transferring information on cholecystokinin-mediated satiation.


Developing a Legal Framework for Advance Healthcare Planning: Comparing England & Wales and Ireland.
This article examines the legislative frameworks for advance healthcare planning in England & Wales (the Mental Capacity Act 2005) and in Ireland (the Assisted Decision-Making (Capacity) Act 2015), undertaking a comparative analysis of each measure, with particular focus on the detail of the approaches taken. It is only through this kind of detailed focus that the normative choices made by legislation can fully be understood and evaluated. The article argues that, in several respects, possibly because the drafters were able to reflect lessons learned from other jurisdictions, the Assisted Decision-Making (Capacity) Act 2015 provides a more rounded and complete form of advance healthcare planning than that provided by the Mental Capacity Act. This is on the basis that it provides more protection for patient choice; better potential for delivery on the choices made; and a more appropriate balance between formalities and enforceability.