Use of a Steerable Sheath for Completely Femoral Access in Branched Endovascular Aortic Repair Compared to Upper Extremity Access.
To compare bridging stent graft (BSG) implantation in downward oriented branches in branched endovascular aortic repair (bEVAR), using a commercially available steerable sheath from an exclusively femoral access (TFA) with traditional upper extremity access (UEA). In a retrospective cohort study, 7 patients with 19 branches in the TFA cohort received BSG insertion using the Medtronic Heli FX steerable sheath from a femoral access, and 10 patients with 32 branches in the UEA cohort from a brachial approach. Technical success, total intervention time, fluoroscopy time, branch cannulation time, and complication rate were recorded. Technical success was 19/19 branches in the TFA and 31/32 in the UEA cohort. The mean branch cannulation time was considerably shorter in the TFA group (17 vs. 29 min, p = 0.003), and total intervention time tended to be shorter (169 vs. 217 min, p = 0.176). Using a commercially available steerable sheath allowed successful cannulation of all branches in this cohort and was associated with significantly shorter branch cannulation times. Potentially, this technique can lower the stroke and brachial puncture site complication risk as well as reduce total intervention time and radiation dose. 2b, retrospective cohort study.


Sacral ectopic phallus in a case of extreme penoscrotal transposition and bladder agenesis.
This is the first report of a surviving male patient with several rare anomalies including a sacral ectopic phallus, extreme penoscrotal transposition, solitary duplex kidney, and bladder agenesis.


Effect of intensive versus moderate lipid-lowering therapy on epicardial adipose tissue in hyperlipidemic post-menopausal women: a substudy of the BELLES trial (Beyond Endorsed Lipid Lowering with EBT Scanning).
This study sought to evaluate the effect of intensive and moderate statin therapy on epicardial adipose tissue (EAT). EAT has been associated with coronary artery disease severity and outcome. It is currently unknown whether EAT volume changes over time when patients are exposed to statin therapy. Subanalysis of a randomized study of atorvastatin 80 mg/day versus pravastatin 40 mg/day for 1 year in a clinical trial designed to assess the progression of coronary artery calcium (CAC) in hyperlipidemic post-menopausal women. Patients underwent cardiac computed tomography scans at the start and end of the trial period. Of 420 patients, 194 received atorvastatin and 226 pravastatin; the median low-density lipoprotein change was -53.3% and -28.3% with atorvastatin and pravastatin, respectively (p < 0.001). Baseline EAT correlated with age, body mass index, hypertension, diabetes mellitus, high-density lipoprotein, triglyceride levels, and CAC (p < 0.001). At the end of follow-up, EAT regressed more in the atorvastatin than in the pravastatin group (median, -3.38% vs. -0.83%, p = 0.025). The EAT percent change from baseline was significant in the atorvastatin, but not the pravastatin group (p < 0.001 and p = 0.2, respectively). There was no correlation between lipid lowering and EAT regression. CAC progressed significantly in both groups from baseline. In hyperlipidemic post-menopausal women, statin therapy induced EAT regression, although intensive therapy was more effective than moderate-intensity therapy. This effect does not seem linked to low-density lipoprotein lowering and may be secondary to other actions of statins such as anti-inflammatory effects.


Infection as a cause of death in the extremely-low-birth-weight infant.
To determine the causes of neonatal death for extremely-low-birth-weight (ELBW) infants. All liveborn infants below 1000 g birth weight born from 1994 to 1998 who died and were autopsied were included. Maternal and infant characteristics, placental histology, autopsy material and culture results were obtained. A total of 263 ELBW infants were born alive, 104 (40%) died and 44 (42%) were autopsied. Placentas were available for 41 (93%). Infection was the leading cause of death in the autopsied babies (25/44; 57%). Sixteen (64%) of these deaths occurred within the first 48 h and were classified as being due to congenital infections. Twenty-two of 41 (54%) placentas showed evidence of infection. Infection as a cause of death peaked at 22 weeks. Other causes of death were lethal anomalies (20%), respiratory distress and its complications (9%) and immaturity, intraventricular hemorrhage and other conditions (14%). Congenital infection is the leading cause of death in ELBW infants.


Face recognition in children with a pervasive developmental disorder not otherwise specified.
This study investigates the accuracy and speed of face recognition in children with a Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS; DSM-IV, American Psychiatric Association [APA], 1994). The study includes a clinical group of 26 nonretarded 7- to 10-year-old children with PDDNOS and a control group of 65 normally developing children of the same age. Two computerized reaction time tasks were administered: a face recognition task and a control task designed to measure the recognition of abstract visuospatial patterns. The latter were either easy or difficult to distinguish from a set of alternative patterns. The normally developing children recognized the faces much faster than the hardly distinguishable abstract patterns. The children in the PDDNOS group needed an amount of time to recognize the faces that almost equalled the time they needed to recognize the abstract patterns that were difficult to distinguish. The results suggest that, when processing faces, children with PDDNOS use a strategy that is more attention-demanding and, hence, less automatic or "Gestalt-like" than the one used by the control children. The results are discussed in the light of a theory that explains the development of coherent mental representations.


The endosomal escape vehicle platform enhances delivery of oligonucleotides in preclinical models of neuromuscular disorders.
Biological therapeutic agents are highly targeted and potent but limited in their ability to reach intracellular targets. These limitations often necessitate high therapeutic doses and can be associated with less-than-optimal therapeutic activity. One promising solution for therapeutic agent delivery is use of cell-penetrating peptides. Canonical cell-penetrating peptides, however, are limited by low efficiencies of cellular uptake and endosomal escape, minimal proteolytic stability, and toxicity. To overcome these limitations, we designed a family of proprietary cyclic cell-penetrating peptides that form the core of our endosomal escape vehicle technology capable of delivering therapeutic agent-conjugated cargo intracellularly. We demonstrated the therapeutic potential of this endosomal escape vehicle platform in preclinical models of muscular dystrophy with distinct disease etiology. An endosomal escape vehicle-conjugated, splice-modulating oligonucleotide restored dystrophin protein expression in striated muscles in the mdx mouse, a model for Duchenne muscular dystrophy. Furthermore, another endosomal escape vehicle-conjugated, sterically blocking oligonucleotide led to knockdown of aberrant transcript expression levels in facioscapulohumeral muscular dystrophy patient-derived skeletal muscle cells. These findings suggest a significant therapeutic potential of our endosomal escape vehicle conjugated oligonucleotides for targeted upregulation and downregulation of gene expression in neuromuscular diseases, with possible broader application of this platform for delivery of intracellular biological agents.


Total body water measurement using bioelectrical impedance analysis, isotope dilution and total body potassium: a scoring system to facilitate intercomparison.
(1) To develop a scale that is useful in evaluating the accuracy of multifrequency bioelectrical impedance analysis (MF-BIA) in the assessment of body water volumes against the accepted gold standard measurements based on isotope-dilution and total body potassium (TBK). (2) To perform a pilot test of the scale. A scale was developed to evaluate the accuracy of MF-BIA in the assessment of body water volumes. Questions were obtained from reading the scientific literature and discussions involving the four authors. Three of these and two additional independent readers pre-tested the scale. A weighting was identified for each question and a pilot test with a sample of 10 articles (different to those used for the questionnaire performance) was conducted. A further validation was carried out with a second set of 20 articles and two additional independent readers. The kappa statistic expressing the level of agreement between pairs of the first three authors using this scale with 10 articles, was 0.3, 0.4 and 0.6 after the first attempt. A second evaluation after specific changes improved the agreement to 0.8, 0.6 and 0.8. The mean score for 10 articles was 252+/-36 points from a total score of 400 (63+/-9%). The evaluation with the second set of 20 articles resulted in a kappa of 0.7 from two pairs of authors. The evaluation with two additional reviewers resulted in a kappa=0.7. A tool has been developed to assess the accuracy of the MF-BIA technique and to identify methodological components, plan future studies and critically evaluate data in this area. It is likely that this tool may also be used to assess the accuracy of single frequency studies.


Recognition and characteristics of concussions in the emergency department population.
An anonymous survey was conducted over a 6-month period of time using consenting Emergency Department (ED) patients in an attempt to better understand concussions occurring in the ED population. Calculations were made using the respondents' history and self-reported symptoms during the previous 12 months. Five hundred twenty-two of 700 approached patients responded to the anonymous questionnaire. Of respondents, 20.1% (105/522) answered that they had experienced symptoms of a concussion after being hit in the head during the previous 12 months. Of the 105 respondents who experienced a concussion, 88.6% (93/105) did not recognize that they had suffered a concussion. There were 28.2% (147/522) of all respondents who were actively engaging in at least one activity that was considered to be at high risk for concussions. Headache was the most common symptom for both recognized and unrecognized concussions. Respondents who experienced nausea after being hit in the head were the most likely to seek some form of medical attention, followed by people who suffered a loss of consciousness. Those patients who suffered a loss of consciousness were the most likely to visit an ED. Many patients have a poor understanding of concussions and these patients may be actively participating in high-risk activities while still suffering symptoms from a concussion. Therefore, these patients may be at risk for further concussions and Second Impact Syndrome.


Octreotide enhances positive calcium balance in Duchenne muscular dystrophy.
Although receptors for somatostatin are found in bone cells, the effect of somatostatin analogs on calcium metabolism is unknown. The authors studied, in a metabolic ward, the effect of octreotide (a long-acting somatostatin analog) and a placebo in two 6-day calcium balance periods in 8 children with Duchenne muscular dystrophy. As expected, octreotide (2 micrograms/kg, subcutaneously, every 8 hours) reduced serum growth hormone and somatomedin (IGF-1) to levels found in growth hormone deficiency. Octreotide enhanced calcium retention by 30% (96 mg daily [P < 0.04]) in 7 boys for whom complete data (diet, urine, and fecal calcium) were available. In 6 children with urinary calcium excretion (Uca) greater than 50 mg daily, octreotide markedly lowered Uca, from 114 +/- 23 mg daily to 61 +/- 9 mg daily (P < 0.03). Calcium retention occurred in patients with or without initial hypercalciuria, but the higher the basal Uca, the greater was the inhibition by octreotide (r = 0.79; P < 0.03). Inactive, nonambulatory patients had a more pronounced response of Uca to octreotide (P < 0.02). Octreotide caused a mild, nonsignificant reduction in fecal calcium, with no major changes in serum calcium, phosphorus, parathyroid hormone, urinary excretion of sodium and potassium, or in creatinine clearance. Based on the current observations and the presence of receptors for somatostatin in bone cells, this hormone may have, at least on a short-term basis, an anabolic effect on calcium, perhaps favoring its deposition in bone.


Cigarette Smoking Motives and Stages of Change in Smoking Cessation Among Veterans: Differences by Gender and Sexual Orientation.
To examine differences across gender and sexual orientation in cigarette smoking motives and stages of change in smoking cessation among Veterans. Secondary data analysis of cross-sectional baseline surveys from a prospective cohort study. United States, self-administered online survey. Cisgender Veterans who reported past-year smoking (N = 146); 66.4% identified as lesbian, gay, or bisexual and 52.1% were men. Smoking motives (i.e., social, self-confidence, boredom relief, and affect regulation), with higher scores indicating stronger motivation to smoke. Stages of change categories included precontemplation, contemplation/preparation, and action/maintenance. Analyses were stratified by gender and sexual orientation. Age-adjusted linear regression models estimated differences in smoking motives scores and multinomial logistic regression models estimated differences in stages of change categories relative to the precontemplation stage (reference category). In this Veteran sample, gay men reported higher social smoking motives vs heterosexual men (β = 1.50 (95% CI: .04, 2.97), P-value = .045) and higher boredom relief smoking motives vs bisexual men (β = 1.53 (95% CI: .06, 2.29), P-value = .041) in age-adjusted models. Lesbian women were more likely to be in the action/maintenance stage relative to the precontemplation stage when compared to both heterosexual women (aRRR = 4.88 (95% CI: 1.00, 23.79) P-value = .050) and bisexual women (aRRR = 16.46 (95% CI: 2.12, 127.57), P-value = .007) after adjusting for age. Smoking cessation interventions may benefit from enhancing peer support for gay men. Given bisexual and heterosexual women were in less advance stages of change, there may be a greater need for motivational interventions to encourage quitting and additional support to assist with cessation efforts. Overall, findings highlight the diversity of cigarette use within LGB communities.


Serial Evaluation of Abdominal Fluid and Serum Amino-terminal pro-C-type Natriuretic Peptide in Dogs with Septic Peritonitis.
Serum N-terminal pro-C-natriuretic peptide (NT-proCNP) has shown promise as a diagnostic biomarker for sepsis. Its sensitivity to detect dogs with septic peritonitis (SP) is reportedly low, perhaps attributable to the compartmentalization of NT-proCNP in the abdominal cavity. To evaluate the use of an ELISA for the measurement of NT-proCNP in canine abdominal fluid and to describe the peri-operative pattern of abdominal fluid and serum NT-proCNP concentrations in dogs with SP. Five client-owned dogs with nonseptic abdominal effusion of varying etiologies and 12 client-owned dogs with SP undergoing abdominal surgery and placement of a closed-suction abdominal drain (CSAD). Six dogs were included upon hospital admission; 6 were included the day after surgery. Prospective pilot study. A commercially available ELISA kit was analytically validated for use on canine abdominal fluid. The NT-proCNP concentrations were measured in the abdominal fluid of control dogs, and in serum and abdominal fluid of dogs with SP from admission for CSAD removal. In dogs with SP, admission abdominal fluid NT-proCNP concentrations were lower than the concurrent serum concentrations (P = 0.031), and lower than control canine abdominal fluid concentrations (P = 0.015). Postoperatively, abdominal fluid NT-proCNP concentrations remained lower than serum concentrations (P < 0.050), except on day 4. The ELISA kit was able to measure NT-proCNP in canine abdominal fluid. In dogs with SP, low serum NT-proCNP concentrations cannot be explained by abdominal compartmentalization.


The long-term differential achievement effects of school socioeconomic composition in primary education: A propensity score matching approach.
The effects of school socio-economic composition on student achievement growth trajectories have been a hot topic of discussion among politicians around the world for many years. However, the bulk of research investigating school socio-economic composition effects has been limited in important ways. In an attempt to overcome the flaws in earlier research on school socio-economic composition effects, this study used data from a large sample, followed students throughout primary education, addressed selection bias problems, identified the grade(s) in which school socio-economic composition mattered the most, and studied the differential effects of school socio-economic composition by individual socio-economic status (SES). In a longitudinal design with seven occasions of data collection, the authors drew on a sample of N = 3,619 students (age at T1 about 5 years, age at T7 about 12 years) from 151 primary schools in Flanders (the northern part of Belgium). Students in low-, medium-, high-, and mixed-SES schools were matched using propensity scores. To compare students' achievement growth trajectories in the different school compositions, multilevel regression modelling with repeated measurements was applied. The results showed that students had more positive achievement growth in high-SES as compared to low-SES and mixed-SES schools. In two of the three comparisons, students in mixed-SES schools showed the lowest math development. The negative effects of mixed-SES schools on math achievement growth were the strongest for high-SES students. Our findings contribute to the ongoing discussion on the effects of school socio-economic composition on student achievement growth.


Cooperative heparin-mediated oligomerization of fibroblast growth factor-1 (FGF1) precedes recruitment of FGFR2 to ternary complexes.
Fibroblast growth factors (FGFs) utilize cell surface heparan sulfate as a coreceptor in the assembly of signaling complexes with FGF-receptors on the plasma membrane. Here we undertake a complete thermodynamic characterization of the assembly of the FGF signaling complex using isothermal titration calorimetry. Heparin fragments of defined length are used as chemical analogs of the sulfated domains of heparan sulfate and examined for their ability to oligomerize FGF1. Binding is modeled using the McGhee-von Hippel formalism for the cooperative binding of ligands to a monodimensional lattice. Oligomerization of FGFs on heparin is shown to be mediated by positive cooperativity (α = 6). Heparin octasaccharide is the shortest length capable of dimerizing FGF1 and on longer heparin chains FGF1 binds with a minimal footprint of 4.2 saccharide units. The thermodynamics and stoichiometry of the ternary complex suggest that in solution FGF1 binds to heparin in a trans-dimeric manner before FGFR recruitment.


Structural Basis for a Unique ATP Synthase Core Complex from Nanoarcheaum equitans.
ATP synthesis is a critical and universal life process carried out by ATP synthases. Whereas eukaryotic and prokaryotic ATP synthases are well characterized, archaeal ATP synthases are relatively poorly understood. The hyperthermophilic archaeal parasite, Nanoarcheaum equitans, lacks several subunits of the ATP synthase and is suspected to be energetically dependent on its host, Ignicoccus hospitalis. This suggests that this ATP synthase might be a rudimentary machine. Here, we report the crystal structures and biophysical studies of the regulatory subunit, NeqB, the apo-NeqAB, and NeqAB in complex with nucleotides, ADP, and adenylyl-imidodiphosphate (non-hydrolysable analog of ATP). NeqB is ∼20 amino acids shorter at its C terminus than its homologs, but this does not impede its binding with NeqA to form the complex. The heterodimeric NeqAB complex assumes a closed, rigid conformation irrespective of nucleotide binding; this differs from its homologs, which require conformational changes for catalytic activity. Thus, although N. equitans possesses an ATP synthase core A3B3 hexameric complex, it might not function as a bona fide ATP synthase.


Infective endocarditis after transcatheter edge-to-edge repair for severe mitral regurgitation; a case report and a systematic review.
Transcatheter edge-to-edge repair (TEER) is used extensively in patients with symptomatic severe mitral regurgitation and high surgical risk. While prosthetic valve endocarditis is well documented, infective endocarditis (IE) after TEER is a rare occurrence. To date, no study has been conducted on this complication. We report the case of an 85-year-old man who developed IE 3 months after undergoing TEER, and we systematically review 26 previously published cases of this complication. Our review findings indicate that discussion within the heart team is essential for the decision-making process and treatment strategy determination.


Experimental studies on the effects of toxic Microcystis aeruginosa PCC7820 on the survival and reproduction of two freshwater rotifers Brachionus calyciflorus and Brachionus rubens.
Blooms of Microcystis aeruginosa frequently occur in many eutrophic lakes in China, however, there is very little experimental study on the relationship between Microcystis and rotifers from Chinese waters. The effects of different concentrations of toxic M. aeruginosa PCC7820 on two common freshwater rotifers Brachionus calyciflorus and B. rubens were investigated in laboratory experiments. B. calyciflorus was able to utilize this strain of M. aeruginosa as a food source. However, M. aeruginosa suppressed the survival and reproduction of B. calyciflorus at the highest concentration (10(6) cells/ml) probably due to the inadequate nutrition. B. rubens was inhibited by toxic M. aeruginosa PCC7820 and the inhibition increased with the increasing Microcystis concentration. Our study indicates that the two rotifers have different sensitivities to toxic M. aeruginosa and that toxic cyanobacteria may affect zooplankton community structure by differentially inhibiting the different zooplankton taxa.


Importance of preemptive analgesia and pain assessment as perceived by intensive care unit nurses.
The importance and efficacy of Preemptive analgesia in reducing pain for patients undergoing painful procedures still debatable and seldom investigated. The aim of this study was to describe intensive care nurses' perception of the importance of pain assessment and Preemptive analgesia prior painful procedures in critical care settings in Jordan. A cross-sectional descriptive design was used. The sample consisted of 300 registered nurses recruited from 22 intensive care units in Jordan. The data was gathered using a self-administered questionnaire. The results showed that nurses considered pain assessment moderately and extremely important for surgical (n = 263, 87.7%), burn (n = 261, 87%), and trauma patients (n = 256, 85.3%). The majority of nurses rated pain assessment as moderately to extremely important for invasive line placement 80.3%, wound care 78.3%, and drain removal 69%. Nurses assessed the need for Preemptive analgesia more frequently before wound care 70.7%, and before invasive line placement 69.7%. Nurses perceived pain assessment for Preemptive analgesia as less priority for unconscious patients. Effective assessment and management of pain for critically ill patients is mandatory. Thus, it is important to improve nurses' knowledge regarding the Preemptive analgesia and its effects in relieving post-procedural pain in critically ill patient. It is recommended to ensure proper clinical training on how to assess critically ill patients and auditing system.


Enabled clinical use of an HIV-1 attachment inhibitor through drug delivery.
The clinical advancement of HIV-1 attachment inhibitors was hindered initially by poor bioavailability. Attempts to identify improved candidates revealed that solubility and dissolution-rate-limited absorption are barriers to achieving adequate antiviral plasma levels. This was mitigated by forming nanosized drugs or by creating stabilised amorphous drug-polymer composites. In further improving drug potency and mitigating solubility-limited bioavailability, a candidate based on a phosphate ester prodrug was identified that, although having excellent bioavailability, exhibited unacceptable pharmacokinetics. Based on in silico modelling and a site of absorption study it was confirmed that creating an extended release formulation could provide the desired pharmacokinetic profile. The optimised formulation showed good antiviral activity when dosed employing a once or twice a day regimen.


Corrigendum: Rigidity and Flexibility in Rotaxanes and Their Relatives; On Being Stubborn and Easy-Going.
[This corrects the article DOI: 10.3389/fchem.2022.856173.].


Background factors and management of ectopic pregnancy in Sweden. Changes over a decade.
Hospital records of all women operated on for ectopic pregnancy (EP) in four Swedish towns during 1970-72 and 1980-82 were elaborated. The gynecological and obstetrical background was noted and the clinical picture and management was recorded and analysed. The incidence of EP more than doubled between the two periods. There was no major change in classical background factors between the periods, but the proportion of IUCD users rose from 4 to 16 percent. The use of hCG assays, curettage and ultrasound in establishing the diagnosis increased markedly and the proportion of women with ruptured tubes and heavy intra-abdominal bleeding decreased. Moreover there was a clear tendency towards a more conservative surgical approach in the latter period.


Acquisition of an appetitive behavior prevents development of stress-induced neurochemical modifications in rat nucleus accumbens.
In rats, exposure to chronic unavoidable stress produces a decrease in dopamine output in the nucleus accumbens shell that is accompanied by a decreased density of the dopamine transporter and an increased activity of the dopamine-D(1) receptor complex. These modifications have been hypothesized to be adaptive to decreased dopamine output in stressed rats. We investigated whether the learning of an appetitive behavior sustained by palatable food, which is associated with increased dopamine output in the nucleus accumbens shell as measured by microdialysis experiments, would affect the modifications induced by chronic stress exposure on dopamine transporter density and dopamine-D(1) receptor complex activity in the nucleus accumbens. Rats exposed to chronic unavoidable stress after acquisition of the appetitive behavior showed a higher dopamine extraneuronal release in the nucleus accumbens shell than that of stressed animals, and similar to that of control rats. Moreover, previous acquisition of the appetitive behavior prevented development of a stress-induced decrease in dopamine transporter density, measured by [(3)H]-WIN 35428 binding, a stress-induced increase in dopamine-D(1) receptor density, measured by binding of [(3)H]-SCH 23390, and SKF 38393-stimulated adenylyl cyclase activity in the nucleus accumbens. These results support the hypothesis that changes induced in pre- and postsynaptic dopaminergic transmission by chronic stress exposure are related to decreased dopamine output.


Dynamics and characterization of Aedes aegypti (L.) (Diptera: Culicidae) key breeding sites.
The present study aimed to analyze the dynamics of containers used as breeding sites by Aedes aegypti (L.) in the city of Aracaju, SE, one of the Northeast Brazilian states. A total of three entomological surveys were performed during different precipitation levels. Breeding sites were categorized according to their function into storage, disposable containers, and reusable containers. "Mean number of pupae" and "frequency of each type of breeding site" were the criteria considered to identify key breeding sites. House index and Breteau index were calculated in each survey. A total of 3,647 water reservoirs were found, of which 220 were breeding sites, where 22,880 immature forms were identified. There were no differences in the mean number of larvae of several types of breeding sites and in the number of larvae among surveys. Larval indices showed a reduction in the second visit, but with no effect on adult occurrence when the number of pupae was considered. Key breeding sites resulted from containers used for water storage. The area studied showed conditions favorable to a new epidemic of dengue fever.


Demonstration of antigenic determinants specific for the split products of the third complement factor, C3.
Crossed anti-C3c immunoelectrophoresis of a plasma sample with in vivo complement activation revealed a pronounced 'spur' formation towards the cathodic region of immunochemical interaction between native C3 and C3c. In situ absorption of the antibody preparation against C determinants of the 3rd complement factor using fresh normal EDTA plasma as antigen demonstrated the presence of C3 split product specific determinants.


Muscle contributions to pre-swing biomechanical tasks influence swing leg mechanics in individuals post-stroke during walking.
Successful walking requires the execution of the pre-swing biomechanical tasks of body propulsion and leg swing initiation, which are often impaired post-stroke. While excess rectus femoris activity during swing is often associated with low knee flexion, previous work has suggested that deficits in propulsion and leg swing initiation may also contribute. The purpose of this study was to determine underlying causes of propulsion, leg swing initiation and knee flexion deficits in pre-swing and their link to stiff knee gait in individuals post-stroke. Musculoskeletal models and forward dynamic simulations were developed for individuals post-stroke (n = 15) and healthy participants (n = 5). Linear regressions were used to evaluate the relationships between peak knee flexion, braking and propulsion symmetry, and individual muscle contributions to braking, propulsion, knee flexion in pre-swing, and leg swing initiation. Four out of fifteen of individuals post-stroke had higher plantarflexor contributions to propulsion and seven out of fifteen had higher vasti contributions to braking on their paretic leg relative to their nonparetic leg. Higher gastrocnemius contributions to propulsion predicted paretic propulsion symmetry (p = 0.005) while soleus contributions did not. Higher vasti contributions to braking in pre-swing predicted lower knee flexion (p = 0.022). The rectus femoris had minimal contributions to lower knee flexion acceleration in pre-swing compared to contributions from the vasti. However, for some individuals with low knee flexion, during pre-swing the rectus femoris absorbed more power and the iliopsoas contributed less power to the paretic leg. Total musculotendon work done on the paretic leg in pre-swing did not predict knee flexion during swing. These results emphasize the multiple causes of propulsion asymmetry in individuals post-stroke, including low plantarflexor contributions to propulsion, increased vasti contributions to braking and reliance on compensatory mechanisms. The results also show that the rectus femoris is not a major contributor to knee flexion in pre-swing, but absorbs more power from the paretic leg in pre-swing in some individuals with stiff knee gait. These results highlight the need to identify individual causes of propulsion and knee flexion deficits to design more effective rehabilitation strategies.


Nonidentity of the 48,000-dalton protein of mRNA-protein particles and the beta subunit of eukaryotic initiation factor 2.
The beta subunits of the GTP-dependent initiator methionyl-tRNA-binding protein and the 48,000-dalton protein, which is one of the two major proteins present in isolated mRNA . protein particles, have been shown to share a number of similar structural and mRNA-binding properties. The nonidentity of these two proteins is now established by documentation of differing molecular weights, isoelectric focusing points, and products of protease or cyanogen bromide cleavage.


A Case Report Highlighting That Silica Gel Products Are Not Always Benign.
Silica gel packets are commonly used desiccants for medication products; these packets generally only pose a choking risk in young children. However, new cylindrical desiccant canisters have been developed, which may increase the risk for obstruction in adults. An elderly male presented to the emergency department complaining of difficulty swallowing after taking his morning medications. Through a diligent work-up a desiccant canister was found lodged in the lower esophageal sphincter. The patient was endotracheally intubated and a Roth Net retriever was used to remove the canister. Cylindrical desiccant canisters pose an increased risk of esophageal obstruction.


Irradiation is an early determinant of endothelial injury during hematopoietic stem cell transplantation.
We investigated the degree and the time course of endothelial injury in mice pretreated with lethal or reduced-intensity irradiation administered before transplantation. Six- to eight-week-old female mice were randomly allocated into three groups: lethal-intensity irradiation (8.5 Gy, group 1), reduced-intensity irradiation (5.0 Gy, group 2), or nonirradiated controls (group 3). After conditioning, circulating endothelial cells (CD31+, CD133(-), and CD45low) and peripheral blood CD4+ or CD8+ T-lymphocyte subpopulations were enumerated using flow cytometry at various times. The morphologic changes in endothelium were examined at phase-contrast light microscopy. Circulating endothelial cells showed an earlier and higher peak in the lethal irradiation group compared with the reduced-intensity irradiation group, which exhibited a protean elevation in cell numbers. There were no visible histopathologic changes during the early stage of endothelial damage. Lethal and reduced doses of irradiation induced endothelial injury in a dose-dependent manner. Endothelial damage may occur before graft-vs-host disease and its related complications.


Photo-oxidative Cross-Dehydrogenative Coupling-Type Reaction of Thiophenes with α-Position of Carbonyls Using a Catalytic Amount of Molecular Iodine.
A metal-free photo-oxidative intermolecular C-H/C-H coupling reaction of thiophenes is demonstrated with carbonyls using a catalytic amount of molecular iodine. In this system, molecular oxygen in the air acted as a terminal oxidant to regenerate molecular iodine. A mechanistic study was also performed.


Liposomes as protective agents of stratum corneum against octyl glucoside: a study based on high-resolution, low-temperature scanning electron microscopy.
The ability of phosphatidylcholine (PC) liposomes to protect pig stratum corneum (SC) against the action of the nonionic surfactant octyl glucoside (OG) was investigated "in vitro" using double-layer coating for high-resolution, low-temperature scanning electron microscopy. This technique has been useful in preventing drying artifacts in the study of biological materials. The treatment of SC with OG led to a perturbation mainly in the corneocytes. However, the incubation of the tissue with liposomes prior to the OG treatment resulted in a progressive decrease in these perturbations and, consequently, in the progressive protection of the SC against the action of the surfactant.


Nitric Oxide in the Prevention of Pre-eclampsia (NOPE): A Double-Blind Randomized Placebo-Controlled Trial Assessing the Efficacy of Isosorbide Mononitrate in the Prevention of Pre-eclampsia in High-Risk Women.
Pre-eclampsia contributes to maternal and fetal morbidity and mortality all over the world. Endothelial dysfunction is postulated to be the crux of the pathogenesis. Recent meta-analysis of aspirin trials showed aspirin to be effective when started early in pregnancy (at ≤ 16-week gestation). We aimed to study the effect of low-dose prophylactic isosorbide mononitrate (ISMN) 20 mg/day on the incidence of hypertensive diseases in high-risk women receiving standard aspirin prophylaxis. Design: Randomized double-blind placebo-controlled parallel-arm superiority trial. Setting: Antenatal clinic of a tertiary teaching hospital, South India. Participants and methods: One hundred women fulfilling NICE guideline criteria for aspirin prophylaxis recruited at 12-16 weeks were randomized to receive either 20 mg/day of ISMN or placebo, in addition to 75 mg/day of oral aspirin from recruitment till delivery. Main outcome measure: Rate of hypertensive disorder of pregnancy (HDP). Sample Size: One hundred women (50 in each arm) to detect a decrease of HDP from 20% in the placebo group to 5% in the ISMN group with a power of 80% and at 0.05. One hundred women (50 in each arm) participated and completed the trial. Intention to treat analysis of these 100 women showed that the groups were comparable in terms of age, BMI, parity, and vascular indices (such as mean arterial pressure, uterine artery pulsatility index, flow-mediated vasodilatation index, brachial-ankle pulse wave velocity, Ankle-Brachial Index, brachial arterial stiffness index, and ankle arterial stiffness index). The rate of hypertensive disorders (gestational hypertension, pre-eclampsia, or superimposed pre-eclampsia) was not significantly different between the groups (14/50, 28% in ISMN vs. 12/50, 24% in placebo group; p = 0.7). The mean gestational age at diagnosis of hypertensive disease (35.4 vs. 36 weeks, ISMN vs. placebo groups, p = 0.7) or the rate of severe disease (8/50, 16% in ISMN vs. 7/50, 14% in the placebo group; p = 0.9) did not differ significantly between the two groups. Stillbirths (1 vs. 2), NICU admission rates (18 vs. 10%), and neonatal mortality (2 vs. 2) were also similar between the groups. The results of the randomized controlled trial of nitric oxide in the prevention of pre-eclampsia (NOPE) showed that in high-risk women receiving standard aspirin prophylaxis from less than 16 weeks, there is no significant reduction in the incidence of hypertensive disorders of pregnancy in the ISMN group, to the desired extent. There was no significant effect on the severity of disease, gestational age at diagnosis of disease or maternal-perinatal morbidity due to low-dose isosorbide mononitrate.


Predicting post stent fractional flow reserve virtually from quantitative flow ratio - Can we really get there from here?
This study compared virtual (residual) post-PCI QFR and actual post-PCI QFR from pre- and post-stent angiograms in predicting post-PCI FFR. While there was no difference in mean values, compared with post-PCI FFR, the post-PCI QFR correlated better than residual QFR. As the CFD algorithms improve, post-PCI QFR can potentially serve as a quality control after PCI to reduce post-PCI angina and adverse outcomes.


Traumatic cervical spinal cord injury with "negative" cervical spine CT scan.
A 46-year-old man fell four steps, striking his neck and having associated neck pain and discomfort. He was evaluated at a local emergency department and reported no neurological deficit but focal mid cervical tenderness. Radiographs and computed tomography (CT) scan were "negative" for cervical spine fracture, dislocation or pre-vertebral soft tissue swelling. He was discharged home in a cervical collar with a scheduled outpatient follow-up. Over the proceeding hours neurologic deterioration occurred, including hand and lower limb weakness with the inability to urinate. The patient returned to the local emergency room and was transferred to a tertiary care hospital where examination revealed C5ASIAB deficits. Repeat high resolution CT scan of the cervical spine with reformatted images was unremarkable for osseous fractures except some loss of definition in the posterior cervical musculature. Emergency magnetic resonance imaging MRI revealed a subluxation of C5/6 right facet (not evident on CT) with disruption of the posterior longitudinal ligament, ligamentum flavum, and disc space with abnormal T2 weighted spinal cord hyperintense signal at C5/6. He underwent emergency C5-C6 anterior and posterior decompression and fusion. One week later an examination showed improved C5ASIAD. This case reveals the difficulty of assessing the cervical spine for instability and potential limitations of current management schemes.


Intracranial dissemination of an ACTH secreting pituitary neoplasm--a case report and review of the literature.
A 52-year-old woman developed recurrent hypercortisolism 3 yr after successful surgical treatment of Cushing's disease. At postmortem, eosinophilic pituitary tissue showing positive ACTH immunohistochemical staining was present in the frontal lobe and cerebellum but there was no tumor in the sella. In the absence of a pituitary tumor, extrasellar ACTH producing tissue could arise from seeding of the cerebrospinal fluid with tumor cells at the time of operation or from an atypical pituitary carcinoma. In this report we review the mechanisms of intracranial dissemination of pituitary tissue and ACTH-secreting pituitary carcinomas, including parasellar invasion, meningeal seeding, and cerebrospinal and hematogenous spread.


[Perilunate dislocations and fracture-dislocations of the wrist, a review of 17 cases].
The authors present the results of a retrospective series of 17 cases of dislocations or perilunate fracture-dislocations of the carpus, treated in emergency (period of less than 7 days). The objective aim of our study was to evaluate the radioclinical fate prognosis of these lesions pathologies and their social commitment impact. It is a retrospective study covering the period from July 2004 to December 2009 (or 54 months). Were included in the study, patients hospitalised for a pure dislocation or a perilunate fracture-dislocation authenticated confirmed by an x-ray postero-anterior and lateral views were included. The series included 15 men and two women, nine manual workers, with an average age of 38.9 years. Based on Herzberg radiological classification, the series included six pure perilunate dislocations (35%) and 11 fracture-dislocations (59%) including seven forms trans-scapho-perilunate and four fractures of the lower end of radius. On the profile x-ray, 16 of the lesions were posterior displacement, including 12 stages I lesions (lunatum in place under the radius), and four stage II (lunatum dislocated in front of the radius). A patient had an anterior dislocation stage II, associated with a radial styloid fracture. All patients were operated using surgical treatment, percutaneous, either open pit, or open approaches combining with broaching scapholunate, scaphocapitate and triquetrolunate pinning. Then, an immobilization for 6 weeks was put in place and was performed using a forearm cast. Rehabilitation began as early as the removal of osteosynthesis was done at pin removal. The average decline follow-up in the series was 26 months. The mean score of Cooney was 63/100. There were two excellent results, two good results, seven middle moderate results, and six bad results. The average Quick-DASH score was 24.6/55 and the PRWE 41/150. The average duration of the work stoppage leave was 8 months, including one retired. The average of flexion-extension arc of the traumatized side was 77% (101°) in comparison to the healthy side. The average strength of the traumatized side was 71% (34kg) in comparison with the healthy side. The average radial-ulnar tilt arc of the traumatized side was 67% (37°) in comparison with the healthy side. There is no formal radioclinical prognostic in the radioclinic correlation. However, it seems to emerge that the timing and the type of support treatment bear the most important prognostic guarantors of a better result factors. Perilunate fracture-dislocations have major arthrogeneous arthrogenic potential, yet with a despite functional outcome consistent allowing resumption of recovery of past previous activities. It would seem that perilunate fracture-dislocations have a better functional outcome than those of pure dislocations. Thus, this work is the beginning of a long-term study, including a larger number of patients.


Serial right ventricular endomyocardial biopsy in rapid-onset severe heart failure due to giant cell myocarditis.
Giant cell myocarditis (GCM) is a serious condition that warrants immediate diagnosis and treatment. It often presents as rapidly progressive heart failure and/or malignant ventricular arrhythmias. Here, we describe a 34-year-old patient with myasthenia gravis who presented with GCM 2 weeks after resection of a thymoma. A cardiac biopsy confirming the diagnosis was done within 3 days after admission. After institution of an aggressive immunosuppressive drug regimen, implantation of an implantable cardioverter defibrillator, and intensive cardiac rehabilitation, the patient recovered dramatically. In control biopsies after 4 weeks and 6 months, no more giant cells were found. We conclude that, in the case of nonischemic acute heart failure in young patients, a biopsy should be performed as soon as possible to prevent an unfavourable outcome of this often fatal disease.


Use of Cyclo-Oxygenase Inhibitors Is Not Associated with Clinical Relapse in Inflammatory Bowel Disease: A Case-Control Study.
Patients with inflammatory bowel disease (IBD) often have associated conditions, for which anti-inflammatory medication with cyclo-oxygenase (COX) inhibitors may be helpful. The current evidence is conflicting regarding the role of COX-inhibitors in causing relapse in IBD. This case-control study examined the association between the use of COX inhibitors and relapse of IBD. Logistic regression was used to analyse the relationship between COX-inhibitors and IBD relapse. Overall COX inhibitor use (combined non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 agents) had a negative association with relapse of IBD (adjusted OR 0.26, 95% CI 0.09-0.80). This negative association was confined to ulcerative colitis (UC) (adjusted OR = 0.06, 95% CI 0.01-0.50) and no association was found in Crohn's disease (CD) patients (adjusted OR 1.25, 95% CI 0.18-7.46). The significant negative association between UC relapse and medication use was also seen with non-specific NSAIDs. Selective COX-2 inhibitor use was rare but non-significantly more common in stable patients. There was no association between low-dose aspirin or paracetamol use and relapse of CD or UC. We conclude that COX-inhibitor use was not associated with an increased risk of relapse in UC or CD, and may be protective in UC. Where indicated, NSAIDs should not be withheld from IBD patients.


Episodic depersonalization in focal epilepsy.
In this report a patient with episodic depersonalization is described. As the depersonalization episodes had been attributed to partial seizures, this patient was treated with antiepileptic medication. However, clinical evaluation with long-term video/EEG revealed no evidence of seizure activity during the depersonalization episodes. On the other hand, further evaluation revealed findings that are frequently associated with focal epilepsy. In addition to episodic depersonalization, this patient had secondary generalized seizures. The relationship between episodic depersonalization, temporal lobe pathology, and epilepsy is discussed against the background of this case.


Li2 MnSnSe4 : A New Quaternary Diamond-Like Semiconductor with Nonlinear Optical Response and Antiferromagnetic Property.
A new selenide with a diamond-like structure, Li2 MnSnSe4 , was synthesized for the first time by using a conventional high-temperature solid-state reaction method. Li2 MnSnSe4 crystallizes in the space group Pmn21 (no. 31) of the orthorhombic system. Its three-dimensional framework is constructed by corner-sharing LiSe4 , MnSe4 , and SnSe4 tetrahedra. The title compound has been discovered to have both type I phase-matchable behavior and to exhibit moderate powder second-harmonic generation intensity, about 0.5 times that of commercial AgGaS2 in the particle size of 200-250 μm at a laser radiation of 2.09 μm. In addition, Li2 MnSnSe4 exhibits congruent melting behavior, which makes the bulk single-crystal growth by the Bridgman-Stockbarger method possible. The temperature-dependent susceptibility measurement indicates an antiferromagnetic interaction with a Néel temperature (TN ) of 8.6 K for this compound.


Are Patients with Syndromic Craniosynostosis at Greater Risk for Epilepsy than Patients with Nonsyndromic Craniosynostosis?
The aim of this study was to determine whether patients with syndromic craniosynostosis (SCS) are at increased risk for epilepsy relative to patients with nonsyndromic craniosynostosis (NSCS). A retrospective cohort study was completed using the Kids' Inpatient Database (KID). All patients diagnosed with craniosynostosis (CS) were included. The primary predictor variable was study grouping (SCS vs. NSCS). The primary outcome variable was a diagnosis of epilepsy. Descriptive statistics, univariate analyses and multivariate logistic regression were performed to identify independent risk factors for epilepsy. The final study sample included a total of 10,089 patients (mean age, 1.78 years ± 3.70; 37.7% female). 9278 patients (92.0%) had NSCS, and the remaining 811 patients (8.0%) had SCS. A total of 577 patients (5.7%) had epilepsy. Not controlling for other variables, patients with SCS were at increased risk for epilepsy relative to patients with NSCS (OR 2.1, P < 0.001). After controlling for all significant variables, patients with SCS were no longer at increased risk for epilepsy relative to patients with NSCS (OR 0.73, P = 0.063). Hydrocephalus, Chiari malformation (CM), obstructive sleep apnea (OSA), atrial septal defect (ASD), gastro-esophageal reflux disease (GERD) were all independent risk factors (P < 0.05) for epilepsy. Syndromic craniosynostosis (SCS) in itself is not a risk factor for epilepsy relative to NSCS. The greater prevalence of hydrocephalus, CM, OSA, ASD, and GERD, all of which were risk factors for epilepsy, in patients with SCS relative to patients with NSCS likely explains the greater prevalence of epilepsy in SCS relative to NSCS.


'Benched' the effect of the COVID-19 lockdown on injury incidence in sub-elite football in Australia: a retrospective population study using injury insurance records.
The primary aim of this study was to compare injury rates pre- and post-COVID-19 lockdown in sub-elite football (soccer) players by analysing the full season and the first month of each season between 2018 and 2020. Secondary aims were to describe the incidence, location and type of injuries and to compare injuries by age group and sex. Descriptive epidemiological study. A de-identified insurance database was retrospectively coded using the Orchard Sports Injury Classification System. Injury incidence per 1000 hours as well as incidence rate ratios (IRR) with confidence intervals were calculated. No significant difference was found in the overall incidence rate in 2020 compared with the 2018 and 2019 seasons (IRR, 1.04 [95% CI, 0.96-1.13]; p = 0.294). However, overall injuries increased by 26% (IRR: 1.26 [95% CI 1.07-1.47]; p < 0.005) and joint sprains increased by 45% (IRR: 1.45 [95% CI 1.14-1.84]; p < 0.005) in the first month of 2020 compared with 2018-2019. Between 2018 and 2020, there were 4149 injury insurance claims, with anterior cruciate ligament (ACL) ruptures accounting for 19% of all injuries. When comparing sex, female players had significantly more ankle sprains whilst male players suffered more dental injuries. This study adds to a growing body of evidence investigating injury rates post-COVID-19 lockdowns in sport. Sub-elite players appear to be at higher risk of joint injuries within the first month of training following a period of lockdown. Overall, stakeholders involved in sub-elite football should prioritise knee and ankle joint injury prevention.


Distribution of local axon collaterals of mitral, displaced mitral, and tufted cells in the rabbit olfactory bulb.
To determine the projection fields of intrabulbar axon collaterals, mitral, displaced mitral, and middle tufted cells in the rabbit olfactory bulb were stained by intracellular injection of HRP. The axon collaterals of mitral cells and displaced mitral cells were distributed exclusively within the granule cell layer (GrL). Those of middle tufted cells were distributed mostly in the GrL and on rare occasions in the mitral cell layer. None of these collaterals entered the external plexiform layer. Axon collaterals of mitral cells, emitted at the depths of the GrL, were distributed widely from the deep portion to the most superficial portion of the GrL. Collaterals of displaced mitral cells were also emitted in the deep part, but they tended to be distributed more superficially in the GrL than mitral cells. Collaterals of middle tufted cells were released and distributed superficially in the GrL. The axon collaterals of these principal cells typically extended for a longer distance than the secondary dendrites, and they sometimes formed bushlike terminal arborizations. The results indicate that the projection fields of the axon collaterals of principal cells are spatially separated from the dendritic projection fields. This suggests that the output of these principal cells through the collaterals has a functionally different role from the output through the dendrites. The observation that the three types of principal cells differ in the distribution pattern of their axon collaterals in the GrL suggests that there is a functional separation of the sublayers in the GrL.


In vitro activities of broad-spectrum cephalosporins against nonmeningeal isolates of Streptococcus pneumoniae: MIC interpretation using NCCLS M100-S12 recommendations.
Publication of the NCCLS M100-S12 document in January 2002 introduced ceftriaxone and cefotaxime MIC interpretative breakpoints of < or =1 microg/ml (susceptible), 2 microg/ml (intermediate), and > or =4 microg/ml (resistant) for nonmeningeal isolates of Streptococcus pneumoniae. To estimate the effect of these breakpoint changes on clinical laboratory susceptibility testing results, nonmeningeal pneumococcal isolate (blood and respiratory) data from The Surveillance Network Database-USA, an electronic surveillance database, for the years 1996 to 2000 were collated and studied. Of 9,863 nonmeningeal isolates tested against ceftriaxone, 82.7% were susceptible, 13.2% were intermediate, and 4.1% were resistant by the M100-S11 NCCLS breakpoints (2001); by M100-S12 breakpoints, 95.9% of the isolates were susceptible, 3.1% were intermediate, and 1.0% were resistant. Of 10,777 nonmeningeal isolates tested against cefotaxime, 79.2% were susceptible, 14.3% were intermediate, and 6.5% were resistant by M100-S11 breakpoints; by M100-S12 breakpoints, 93.5% were susceptible, 4.2% were intermediate, and 2.3% were resistant. Overall, the new M100-S12 ceftriaxone and cefotaxime interpretative breakpoints for nonmeningeal isolates of S. pneumoniae decreased the number of isolates interpreted as intermediate by 10% and as resistant by 3 to 4%.


Phosphatidylinositol 4-kinase β mutations cause nonsyndromic sensorineural deafness and inner ear malformation.
Congenital hearing loss is a common disorder worldwide. Heterogeneous gene variation accounts for approximately 20-25% of such patients. We investigated a five-generation Chinese family with autosomal-dominant nonsyndromic sensorineural hearing loss (SNHL). No wave was detected in the pure-tone audiometry, and the auditory brainstem response was absent in all patients. Computed tomography of the patients, as well as of two sporadic SNHL cases, showed bilateral inner ear anomaly, cochlear maldevelopment, absence of the osseous spiral lamina, and an enlarged vestibular aqueduct. Such findings were absent in nonaffected persons. We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4KB gene (p.Gln121Arg) encoding phosphatidylinositol 4-kinase β (PI4KB) from the patients in this family. In addition, 3 missense PI4KB (p.Val434Gly, p.Glu667Lys, and p.Met739Arg) mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases. No such mutations were present within 600 Chinese controls, the 1000 genome project, gnomAD, or similar databases. Depleting pi4kb mRNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment, mimicking the patient phenotypes. Moreover, overexpression of 4 human missense PI4KB mutant mRNAs in zebrafish embryos resulted in impaired hearing function, suggesting dominant-negative effects. Taken together, our results reveal that PI4KB mutations can cause SNHL and inner ear malformation. PI4KB should be included in neonatal deafness screening.


Noncutaneous Melanomas: A Single-Center Analysis.
The optimal treatment algorithm for noncutaneous melanomas must yet be established. To compare systemic treatment-relevant mutational status, metastatic pattern and response to systemic treatment in noncutaneous melanoma. Retrospective single-center study analyzing 64 noncutaneous melanoma patients treated between January 2006 and September 2013. c-KIT mutations were found exclusively in vulvovaginal melanoma (4/7). Overall status for NRAS and BRAF mutations was low (1/7 and 0/21 detected mutations, respectively). Seven out of 7 vulvovaginal and 6/13 sinonasal melanomas first metastasized to lymph nodes, whereas 18/22 ocular melanomas first metastasized to the liver. Response to systemic treatment in vulvovaginal melanomas was best for imatinib with a disease control rate of 3/3 and overall for ipilimumab with a disease control rate of 3/10. Sorafenib was associated with adverse drug reactions (6/13) and poor results. Noncutaneous melanomas show few tumor-signaling pathway mutations and distinct metastasization patterns. Immunotherapy induces response rates in mucosal melanoma similar to those in cutaneous melanoma.


Histone patterns during early embryogenesis in the euchiuroid Urechis caupo.
Histones were isolated from nuclei of Urechis caupo unfertilized eggs and embryos from early cleavage through gastrula. Polyacrylamide gel electrophoresis showed the presence of a slow migrating H1s fraction in the egg which was replaced by a faster migrating H1 during development. Radioactive labelling showed no synthesis of H1s from fertilization up to gastrula and a high rate of synthesis of H1 relative to the other histones during cleavage and blastula stages.


Systematic review of perioperative use of immunosuppressive agents in patients undergoing bariatric surgery.
Patients who qualify for bariatric surgery are increasingly experiencing co-morbid conditions, which often require management through the use of immunosuppressive agents, such as corticosteroids, tumor necrosis factor-alpha inhibitors, or other immunomodulators, which may increase the risk of infection or wound healing complications. Perioperative management of these agents in bariatric surgery is challenging because of the lack of research in this patient population. With the use of immunosuppressive agents on the rise, the effects of these medications must be understood, both the risks posed in the perioperative period, and the benefit their sustained use may have for co-morbidity management. To describe the safety of immunosuppressive agents prior to bariatric surgery. United States of America. A systematic review was conducted to answer these questions about commonly encountered immunosuppressive agents. This review includes information from 37 studies to present recommendations and reasoning for the discontinuation and postoperative reinitiation of immunosuppressive agents including, tumor necrosis alpha factor-a inhibitors, methotrexate, and more. Research addressing complications of these medications in patients undergoing bariatric surgery is sparse. Information from abdominal or general surgical complications may serve as a basis for conservative recommendations. Data specific to each agent or class are presented below. The use of these agents may be critical for patients' chronic disease management, and the consequences of their impact should be considered by bariatric surgeons. While their immune system effects ultimately lead to disease management, each agent must be handled individually due to the varying effects and the potential for perioperative untoward effects.


Phosphorylation of androgen receptor serine 81 is associated with its reactivation in castration-resistant prostate cancer.
Phosphorylation of serine 81 (pS81) in the N-terminal transactivation domain of the androgen receptor (AR) has been linked to its transcriptional activation in prostate cancer (PCa) cell lines, but in vivo studies have been limited. Moreover, the role of pS81 in the reactivation of AR when tumors relapse after androgen deprivation therapy (castration-resistant prostate cancer, CRPC) has not been determined. In this study we validate a pS81 antibody for immunohistochemistry (IHC) and show it yields strong nuclear staining in primary PCa clinical samples and in the VCaP PCa xenograft model. Moreover, this staining was decreased at 7 days post-castration in VCaP xenografts, coinciding with markedly decreased AR transcriptional activity. Staining with the pS81 antibody then was restored when the VCaP xenografts relapsed, which was associated with restoration of AR transcriptional activity. Significantly, analysis of CRPC clinical samples, including tumors that had progressed during treatment with abiraterone, showed strong nuclear staining with the pS81 antibody. Together these findings indicate that AR reactivation in CRPC is associated with S81 phosphorylation, and suggest that IHC for pS81 may be useful as a biomarker of AR activity in CRPC.


Immunocytochemical demonstration of taurine.
Amino acid immunocytochemistry represents a new and powerful tool in neuroscience. Antisera are now available to a large number of amino acids, including those that are thought to serve a transmitter role. The antiserum described here against conjugated taurine seems to be of good specificity and can be used to demonstrate taurine in the CNS as well as in other organs; in normal tissue and in experimental and pathological conditions.


Microwave imaging for neoadjuvant chemotherapy monitoring: initial clinical experience.
Microwave tomography recovers images of tissue dielectric properties, which appear to be specific for breast cancer, with low-cost technology that does not present an exposure risk, suggesting the modality may be a good candidate for monitoring neoadjuvant chemotherapy. Eight patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer were imaged longitudinally five to eight times during the course of treatment. At the start of therapy, regions of interest (ROIs) were identified from contrast-enhanced magnetic resonance imaging studies. During subsequent microwave examinations, subjects were positioned with their breasts pendant in a coupling fluid and surrounded by an immersed antenna array. Microwave property values were extracted from the ROIs through an automated procedure and statistical analyses were performed to assess short term (30 days) and longer term (four to six months) dielectric property changes. Two patient cases (one complete and one partial response) are presented in detail and demonstrate changes in microwave properties commensurate with the degree of treatment response observed pathologically. Normalized mean conductivity in ROIs from patients with complete pathological responses was significantly different from that of partial responders (P value = 0.004). In addition, the normalized conductivity measure also correlated well with complete pathological response at 30 days (P value = 0.002). These preliminary findings suggest that both early and late conductivity property changes correlate well with overall treatment response to neoadjuvant therapy in locally advanced breast cancer. This result is consistent with earlier clinical outcomes that lesion conductivity is specific to differentiating breast cancer from benign lesions and normal tissue.


Development of a potassium ion-selective fluorescent sensor based on 3-styrylated BODIPY.
We have developed a red-emitting fluorescent K(+) probe, B3TAC, which also shows a wavelength shift upon binding to K(+). The probe was synthesized by conjugating a cryptand-based chelator, 2-triazacryptand [2,2,3]-1-(2-methoxyethoxy)benzene (TAC), to position 3 of the BODIPY fluorophore through a styryl linker. In water-acetonitrile mixed solvent, it responded to K(+) in the physiological concentration range with high selectivity over Na(+) and other metal ions. B3TAC is potentially useful for measuring cellular K(+) ion concentration, as well as for simple, naked-eye detection of K(+) in solution.


Nurses' spiritual well-being and the COVID-19 pandemic: A thematic approach.
This study explores nurses' perceived spiritual well-being in the workplace during the COVID-19 pandemic. Nurses have been working heavy shifts under challenging workplace conditions during the COVID-19 pandemic, leading to anxiety and psychological stress. These various challenges at work place their spiritual well-being at risk. An unstructured individual online interview was conducted to collect data from 18 nurses from April to August 2021. Data were analysed using the thematic approach. This study highlighted the four themes of spiritual well-being of nurses, namely, "Trust in God," "spiritual encouragement," "spiritual attributes in the workplace," and "spiritual growth." The study concludes that spirituality is critical in helping nurses overcome the myriad of adversities they face as they assume their important roles during the ongoing pandemic. The study emphasizes that nurses' spiritual aspect during crises is equally important with the other aspects of a nurse's life. Moreover, policies and interventions in hospitals must be implemented to ensure excellent levels of spiritual well-being among nurses.


Pregnancy and the Ehlers-Danlos syndrome: a retrospective study in a Dutch population.
The study was carried out to assess the course and outcome of pregnancies in women with the Ehlers-Danlos syndrome, with the aim of developing guidelines for assessment of risk and counseling, and for providing optimum medical and obstetric care. A retrospective study based on data collected from members of the Dutch Association of Ehlers-Danlos patients. Pregnancies and neonatal outcomes of the affected mothers were compared with those of the nonaffected mothers who delivered an infant with Ehlers-Danlos syndrome. In a group of 46 women with Ehlers-Danlos syndrome, 128 pregnancies beyond 24 weeks gestation were evaluated and compared with 43 pregnancies of 33 nonaffected women. The main maternal complications consisted of pelvic pain and instability (26% vs. 7%). One bowel rupture was reported in a woman with Ehlers-Danlos syndrome type IV. Preterm delivery occurred in 21% of the affected mothers compared with 40% of the nonaffected women with an affected infant; the women with Ehlers-Danlos syndrome experienced postpartum hemorrhage (19% vs. 7%) and complicated perineal wounds (8% vs. 0%) more often than the unaffected women. The floppy infant syndrome was diagnosed in 13% of the affected infants and did not occur in the nonaffected neonates. Pregnancy is generally well-tolerated in women with Ehlers-Danlos syndrome, with favorable maternal and neonatal outcomes. In Ehlers-Danlos syndrome type IV it may be associated with severe maternal complications. Preconceptional counseling concerning specific possible complications and a multidisciplinary approach are recommended.


Suicidal behavior in individuals with amyotrophic lateral sclerosis: A systematic review.
Amyotrophic Lateral Sclerosis (ALS) leads to a drastic reduction in quality of life, generating intense psychological distress and predisposing those affected to mental illness and, in more severe cases, suicidal behavior. This is a systematic review aiming to estimate the frequency of wish to die, suicide ideation and suicide in individuals with ALS using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The following databases were used: Pubmed/MEDLINE, PsycINFO, Embase, SciELO, Biblioteca Virtual de Saúde (BVS), and Cochrane Library. The choice of appropriate descriptors, or their equivalents, to define the search terms was based on the technical and scientific vocabulary of each database. 13 articles were included in the present systematic review, of which three were cross-sectional studies, nine were cohort-type and there was one case-control study. The studies show that individuals with ALS have a higher risk of suicide in relation to the general population, and there is evidence that this risk is even higher in the early stages of the disease. Major Depressive Disorder was the most prevalent mental disorder in the studies included. This mental health concern is often undertreated, leading to the increased susceptibility of this population to suicide. In general, the study samples represent a highly heterogeneous population while many instruments used in the data collection were not uniform. The high degree of psychological vulnerability of this population, associated with a greater predisposition to suicidal behavior, should be minimized through public health measures.


Discharge patterns of baroreceptor-modulated neurons in the nucleus tractus solitarius.
Activity of baroreceptor-modulated neurons in the nucleus tractus solitarius (NTS) was recorded extracellularly during selective pressure stimulation of carotid baroreceptors, using an isolated carotid sinus preparation in anesthetized dogs. One of two different patterns of activity was recorded from individual baro-sensitive neurons in response to slow ramp increases in carotid sinus pressure. The cause of these two distinct firing patterns is not known but preliminary results indicate that it may be due in part to input from different functional types of baroreceptors. These results suggest that some differentiation in blood pressure control may be encoded in the responses of central baro-sensitive neurons in the NTS.


Effects of SOA and flash pattern manipulations on ERPs, performance, and preference: implications for a BCI system.
P3 brain-computer interfaces (BCIs) are synchronous communication systems that allow users to communicate interest in a target event by choosing to attend to it while ignoring other events. In such a system, a cogneme refers to the user's response to: "/attend to the event/" or "/ignore the event/". The present study examined subjects' ability to generate more cognemes per minute (by varying stimulus onset asynchrony or SOA), or requiring fewer cognemes to convey a message (by varying the pattern of stimulus presentation). Both of these have implications for improved information throughput in a P3 BCI. SOAs of 125, 250, and 500 ms were used. Additionally, the conventional "single flash" approach was compared to a new "multiple flash" condition in which half of the stimuli in an 8 x 8 grid were flashed simultaneously. In both conditions, P3-like component amplitudes decreased with faster SOAs at low target probabilities, but the trend did not hold for higher probabilities. The multiple flash condition produced more robust ERPs at the faster speeds. The results also indicate that attend/ignore differences were more apparent following multiple flashes for low target probabilities, but less apparent for high target probabilities. Although information throughput alone does not support the superiority of one approach over the other, only six cognemes are needed in the multiple flash conditions to identify a character, compared to sixteen cognemes in the single flash condition. This suggests that the former approach could operate more rapidly. Thus, the present results suggest that the multiple flash approach may be a more efficient and faster basis for a P3 BCI system.


Role of genetic and molecular profiling in sarcomas.
The treatment of sarcomas has been challenging due to their heterogeneity, rarity in the general population, relative insensitivity to chemotherapeutics, and lack of effective targeted agents. One of the first major breakthroughs in the treatment of sarcomas was the use of imatinib to treat gastrointestinal stromal tumors (GISTs). Since then, advanced molecular techniques and genetic profiling have revolutionized the approach to sarcoma classification, diagnosis, prognosis and, most importantly, treatment. As the sarcoma genetic database continues to expand, the basis for how we classify, diagnose, and treat these challenging malignancies will be redefined. The overall goal of these types of techniques has been to determine a molecular blueprint for each sarcoma subtype and discover actionable alterations that lend themselves to targeted therapies. Other important information derived from these large genomic databases includes biomarkers, prognostic indicators, and information regarding tumorigenesis. Eventually, advanced molecular techniques will provide a personalized-medicine approach that tailors each treatment regimen to the patient's own tumor genome.


Gastric pouch carcinoma after gastric bypass for morbid obesity.
The relationship between bariatric surgery and gastric cancer is conjectural. We present a 52-year-old woman with BMI 45 operated initially by a Lap-Band procedure complicated by gastric wall erosion of the band 9 months later. She was re-operated and the band was removed. She subsequently underwent a Roux-en-Y gastric bypass. 5 years after, gastric carcinoma was discovered in the gastric pouch. Because of varied symptoms following bariatric surgery, patients may not present promptly with symptoms related to a gastric carcinoma.


The Value of Hematological Indexes in Evaluating the Risk of Hip Involvement in Patients with Ankylosing Spondylitis.
The goal was to explore the value of neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in evaluating the risk of hip involvement in patients with ankylosing spondylitis (AS). The study included 188 AS patients (Based on BASRI-hip score, patients were classified as hip involvement group (BASRI-hip ≥ 2; n = 84) and non-hip involvement group (BASRI-hip ≤ 1; n = 104), 173 patients with osteoarthritis (OA) of the hip and 181 age- and gender-matched healthy controls (HCs). The value of NLR and MLR in different groups were observed. The NLR and MLR in AS patients with hip involvement were significantly higher than in the non-hip involvement group (p < 0.05), and patients with moderate and severe hip involvement were significantly higher than mild hip involvement (p < 0.05). The analysis of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of NLR, MLR, and the combination of NLR and MLR for AS patients with hip involvement were 0.817, 0.840, and 0.863, respectively (each p < 0.001) and the AUC values for predicting AS patients with moderate and severe hip involvement in patients with AS were 0.862, 0.847, and 0.889, respectively (each p < 0.001), which showed their significance in clinical settings. Also, NLR and MLR of AS patients were positively correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (each p < 0.01). Therefore, NLR and MLR may be diagnostic hematological indexes in evaluating AS patients with hip involvement, particularly in the patients with moderate and severe hip involvement and higher diagnostic efficiency when combined analysis is done.


Thirdhand smoke contamination in hospital settings: assessing exposure risk for vulnerable paediatric patients.
Tobacco has regained the status of the world's number two killer behind heart/vascular disease. Thirdhand smoke (THS) residue and particles from secondhand smoke (SHS) are suspected health hazards (eg, DNA damage) that are likely to contribute to morbidity and mortality, especially in vulnerable children. THS is easily transported and deposited indoors, where it persists and exposes individuals for months, creating potential health consequences in seemingly nicotine-free environments, particularly for vulnerable patients. We collected THS data to estimate infant exposure in the neonatal ICU (NICU) after visits from household smokers. Infant exposure to nicotine, potentially from THS, was assessed via assays of infant urine. Participants were mothers who smoked and had an infant in the NICU (N=5). Participants provided surface nicotine samples from their fingers, infants' crib/incubator and hospital-provided furniture. Infant urine was analysed for cotinine, cotinine's major metabolite: trans-3'-hydroxycotinine (3HC) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the nicotine-derived and tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Incubators/cribs and other furniture had detectable surface nicotine. Detectable levels of cotinine, 3HC and NNAL were found in the infants' urine. THS appears to be ubiquitous, even in closely guarded healthcare settings. Future research will address potential health consequences and THS-reduction policies. Ultimately, hospital policies and interventions to reduce THS transport and exposure may prove necessary, especially for immunocompromised children.


The blood flow velocity waveform in the fetal internal carotid and umbilical artery; its relation to fetal behavioural states in normal pregnancy at 37-38 weeks.
The relation between the blood flow velocity waveform in the fetal internal carotid artery (n = 12) and umbilical artery (n = 15) and fetal behavioural states at 37-38 weeks of gestation was studied. In the fetal internal carotid artery, under standardized fetal heart rate conditions, the pulsatility index (PI), as a measure of peripheral vascular resistance, was significantly lower during behavioural state 2F (active sleep) compared with state 1F (quiet sleep) according to the classification by Nijhuis et al. (1982), suggesting increased fetal cerebral blood flow during state 2F. In the umbilical artery, no significant difference in PI between the two behavioural states could be established. This suggests a fetal origin of the state dependency observed in fetal blood flow velocity waveforms.


Short Bowel Syndrome and Dysmotility.
Due to recent advances, the mortality due to short bowel syndrome (SBS) has significantly decreased, but the morbidities are still high. Morbidities arising specifically due to dysmotility in SBS include feeding intolerance, prolonged dependence on parenteral nutrition, and associated complications such as intestinal failure associated liver disease, and bloodstream infections. The understanding of the pathogenesis of dysmotility in SBS has improved vastly. However, the tools to diagnose dysmotility in SBS in infants are restrictive, and the medical therapies to treat dysmotility are limited. Surgical techniques available for the treatment after failure of conservative management of dysmotility offer hope but carry their associated risks. The evidence to support either the medical therapies or the surgical techniques to treat dysmotility in SBS in children is scarce and weak. Development of newer therapies and efforts to build evidence to support currently available treatments in treating dysmotility in SBS is needed.


Review: Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies.
Accumulating evidence indicates an important pathophysiological role of brain inflammation in epilepsy. In this review, we will provide an update of specific inflammatory pathways that have been proposed to be crucial in the underlying molecular mechanisms of epilepsy, including the interleukin-1 receptor/toll-like receptor signalling, cyclooxygenase-2, tumour necrosis factor-alpha, complement signalling and chemokines. Furthermore, by drawing on evidence from preclinical and clinical studies we will discuss the potential of these signalling pathways targets for novel therapeutic interventions that control drug-resistant seizures or have disease-modifying effects. Finally, we will assess the use of these inflammatory pathways as potential biomarkers for the development of epilepsy or to measure the effectiveness of therapeutic interventions.


HLA-A*24:388N: a novel HLA-A*24 allele identified by sequence-based typing.
The novel allele, A*24:388N, was identified by sequence-based typing in a Chinese individual.


UDP/P2Y6 receptor signaling regulates IgE-dependent degranulation in human basophils.
P2Y purinergic receptors (P2YR) are G protein-coupled receptors that are stimulated by extracellular nucleotides. They mediate cellular effects by regulating cAMP production, protein kinase C activation, inositol trisphosphate generation, and Ca2+ release from intracellular stores. The P2Y6 receptor of this family is selectively stimulated by UDP, and selectively inhibited by MRS2578. In the present study, we examined the effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in human basophils. Basophils were purified from human peripheral blood. The mRNA expression of genes encoding P2YR and ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase) was measured by RT-PCR. Intracellular Ca2+ influx via UDP/P2Y6 receptor signaling in basophils was detected using a calcium probe. The effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in basophils was confirmed by measuring CD63 expression by flow cytometry. Autocrine secretion of nucleotides was detected by HPLC analysis. We showed that purified basophils express P2Y6 mRNA and that UDP increased intracellular Ca2+, which was reduced by MRS2578 treatment. UDP promoted IgE-dependent degranulation. Furthermore, MRS2578 inhibited IgE-dependent degranulation in basophils. HPLC analysis indicated that basophils spontaneously secrete UTP. In addition, basophils expressed the extracellular nucleotide hydrolases ENTPDase2, ENTPDase3, and ENTPDase8. This study showed that UDP/P2Y6 receptor signaling is involved in the regulation of IgE-dependent degranulation in basophils, which might stimulate the P2Y6 receptor via the autocrine secretion of UTP. Thus, this receptor represents a potential target to regulate IgE-dependent degranulation in basophils during allergic diseases.


Identifying prognostic markers in spatially heterogeneous breast cancer microenvironment.
To gain deeper insights into the microenvironment of breast cancer, we utilized GeoMx Digital Spatial Profiling (DSP) technology to analyze transcripts from 107 regions of interest in 65 untreated breast cancer tissue samples. Our study revealed spatial heterogeneity in the expression of marker genes in tumor cell enriched, immune cell enriched, and normal epithelial areas. We evaluated a total of 55 prognostic markers in tumor cell enriched regions and 15 in immune cell enriched regions, identifying that tumor cell enriched regions had higher levels of follicular helper T cells, resting dendritic cells, and plasma cells than immune cell enriched regions, while the levels of resting CD4 memory in T cells and regulatory (Treg) T cells were lower. Additionally, we analyzed the heterogeneity of HLA gene families, immunological checkpoints, and metabolic genes in these areas. Through univariate Cox analysis, we identified 5 prognosis-related metabolic genes. Furthermore, we conducted immunostaining experiments, including EMILIN2, SURF4, and LYPLA1, to verify our findings. Our investigation into the spatial heterogeneity of the breast cancer tumor environment has led to the discovery of specific diagnostic and prognostic markers in breast cancer.


Losses of lifetime employment duration and productivity for patients with different subtypes and stages of lung cancer.
How different subtypes and stages of lung cancer affect morbidity- and mortality-associated productivity have not been investigated. This study quantified the losses of lifetime employment duration and productivity among patients with various subtypes and stages of lung cancer. We identified nationwide lung cancer patients diagnosed at the ages of 50-64 between 2011 and 2019. Monthly survival probabilities were weighted by monthly employed-to-population ratios and working salaries to estimate lifetime employment duration and productivity. We compared lifetime employment duration and productivity of patients with those of the age-, sex-, calendar year-matched general population for losses of lifetime employment duration and productivity, which were multiplied by pathology and stage shifts based on the first-round screening of Taiwan Lung Cancer Screening in Never Smoker Trial (TALENT) to calculate the savings of lifetime employment duration and productivity. Lung cancer patients had shorter survival and employment duration than the referents. Patients with lung cancers other than adenocarcinoma experienced greater losses of lifetime employment duration and productivity as compared to adenocarcinoma patients. Applying the estimations of never-smoking patients to 100 lung cancer patients with pathology and stage shifts based on the TALENT, the savings of lifetime employment duration and productivity were 132.2 (95% prediction interval: 116.2-147.4) years and 3353 (95% prediction interval: 2914-3802) thousand US dollars, respectively. Early diagnosis of lung cancer would save the losses of employment duration and lifetime productivity. Future evaluation of the cost-effectiveness of lung cancer screening could consider incorporating these societal impacts.


Auditory evoked potentials (early, middle, late components) and audiological tests in Friedreich's ataxia.
A functional assessment of the acoustic pathways in a group of 9 patients with Friedreich's ataxia was performed. In none of them was symptomatic auditory impairment noticeable. All patients were submitted to audiological tests and AEP recording. AEPs included early (BAEPs), middle (MLCs) and long (LLCs) latency components. The absence of one or more BAEP waves was observed in 5 out of 9 patients. N85 latency was significantly increased in all but one patient. MLCs, particularly P12, N15, P25 were often normal in amplitude and latency, scarcely showing a positive relationship with abnormalities of preceding and following waves. Pure tone audiometry revealed cochlear or neural impairment only in 2 patients. Speech audiometry showed deficits in all patients. These investigations, taken as a whole, showed a prevalent involvement of the brain-stem acoustic pathways, presumably at different levels, seldom associated with eighth nerve impairment. In some cases LLC (N85) abnormalities could not be interpreted as a consequence of impaired function in peripheral and brain-stem acoustic sites and might suggest a cortical dysfunction. Major BAEP abnormalities were observed in patients with longer disease duration, while N85 changes were unrelated to the duration and the severity of the illness. The former may prove to be a reliable means of monitoring the progression of the disease, the latter could be employed as a complementary procedure in its early diagnosis.


Selective management of gunshot wounds to the neck. Report of a series and review of the literature.
Thirty-two patients with gunshot wounds to the neck, 13 with multiple pellet injuries and 19 with single missile injuries, were managed selectively. Although 3 of the 32 patients died in the hospital, no death was attributable to the neck injury. This experience and a review of the literature support the concept of selective management of penetrating neck injuries with intervention based on specific indications.


Confidence in Assessment of Lumbar Spondylolysis Using Three-Dimensional Volumetric T2-Weighted MRI Compared With Limited Field of View, Decreased-Dose CT.
Limited z-axis-coverage computed tomography (CT) to evaluate for pediatric lumbar spondylolysis, altering the technique such that the dose to the patient is comparable or lower than radiographs, is currently used at our institution. The objective of the study was to determine whether volumetric 3-dimensional fast spin echo magnetic resonance imaging (3D MRI) can provide equal or greater diagnostic accuracy compared with limited CT in the diagnosis of pediatric lumbar spondylolysis without ionizing radiation. Volumetric 3D MRI can provide equal or greater diagnostic accuracy compared with low-dose CT for pediatric lumbar spondylolysis without ionizing radiation. Clinical review. Level 2. Three pediatric neuroradiologists evaluated 2-dimensional (2D) MRI, 2D + 3D MRI, and limited CT examinations in 42 pediatric patients who obtained imaging for low back pain and suspected spondylolysis. As there is no gold standard for the diagnosis of spondylolysis besides surgery, interobserver agreement and degree of confidence were compared to determine which modality is preferable. Decreased-dose CT provided a greater level of agreement than 2D MRI and 2D + 3D MRI. The kappa for rater agreement with 2D MRI, 2D + 3D MRI, and CT was 0.19, 0.32, and 1.0, respectively. All raters agreed in 31%, 40%, and 100% of cases with 2D MRI, 2D + 3D MRI, and CT. Lack of confidence was significantly lower with CT (0%) than with 2D MRI (30%) and 2D + 3D MRI (25%). For diagnosing spondylolysis, radiologist agreement and confidence trended toward improvement with the addition of a volumetric 3D MRI sequence to standard 2D MRI sequences compared with 2D MRI alone; however, agreement and confidence remain significantly greater using decreased-dose CT when compared with either MRI acquisition. Decreased-dose CT of the lumbar spine remains the optimal examination to confirm a high suspicion of spondylolysis, with dose essentially equivalent to radiographs. If clinical symptoms are not classic for spondylolysis, 2D MRI is still very good at detecting spondylolysis while remaining sensitive for detection of alternative diagnoses such as disc abnormalities and pars stress reaction. The data suggest that standard 2D MRI sequences should not be entirely replaced by a volumetric T2-weighted 3D sequence (despite promising features of rapid acquisition time, increased spatial resolution, and reconstruction capability).


Prevalence of fimA genotypes of Porphyromonas gingivalis and other periodontal bacteria in a Spanish population with chronic periodontitis.
The aim of this study was to determine the prevalence of the different fimA genotypes of Porphyromonas gingivalis in adult Spanish patients with chronic periodontitis, patients with gingivitis and periodontally healthy subjects, and the relationship between these genotypes and other periodontopathogenic bacteria. Samples of subgingival plaque were taken from 86 patients (33 with chronic periodontitis, 16 with gingivitis, and 37 periodontally healthy) in the course of a full periodontal examination. PCR was employed to determine the presence of the 6 fimA genotypes of Porphyromonas gingivalis (I-V and Ib) and of Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola. Porphyromonas gingivalis fimA genotypes II and Ib were present in significantly higher percentages in periodontal patients (39.4% and 12.1% respectively) than in healthy or gingivitis subjects. The prevalence of Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis fimA genotype IV was significantly higher in the group that presented bleeding greater than 30%. A positive correlation was found between Porphyromonas gingivalis fimA genotype IV and Treponema denticola. A strong association between Porphyromonas gingivalis fimA genotypes II and Ib and chronic periodontitis exists in the Spanish population. The most prevalent genotype in periodontal patients is II.


Behaviour therapy in clinical child psychiatry: a preliminary report.
This paper reports on the practice of behaviour therapy with children and families in a clinical setting. The behavioural treatment of 33 cases is discussed. The cases are characterized by the range of problems treated and the variety of behavioural techniques used. Behaviour therapy is shown to be an approach that can be used effectively in a variety of different settings and alongside, or together with treatments based on different theoretical orientations.


The Low Density Matter (LDM) beamline at FERMI: optical layout and first commissioning.
The Low Density Matter (LDM) beamline has been built as part of the FERMI free-electron laser (FEL) facility to serve the atomic, molecular and cluster physics community. After the commissioning phase, it received the first external users at the end of 2012. The design and characterization of the LDM photon transport system is described, detailing the optical components of the beamline.


[Humoral immune response--cervical cancer patients: lymphocytotoxic antibodies (author's transl)].
Sera of 120 cervical cancer patients as well as that of 116 healthy control persons were screened for lymphocytotoxic antibodies using microlymphocytotoxic tests variated in temperature and incubation time. In 76 of 120 cancer-sera (63.3%) lymphocytotoxic antibodies could be detected in comparison with 26 sera of 116 controls (22.4%); p less than 0.0005. With the differentiation into the stages of the disease the highest percentage of lymphocytotoxic antibodies was found in patients with stage 0 of cervical cancer. The presence of lymphocytotoxic antibodies in sera of cervical cancer patients suggest the possibility that this disease is an allotransplant as well as expression of an autoimmune process.


Plasma matrix metalloproteinase-3 predicts mortality in acute respiratory distress syndrome: a biomarker analysis of a randomized controlled trial.
Matrix metalloproteinase-3 (MMP-3) is a proteolytic enzyme involved in acute respiratory distress syndrome (ARDS) pathophysiology that may serve as a lung-specific biomarker in ARDS. This study was a secondary biomarker analysis of a subset of Albuterol for the Treatment of Acute Lung Injury (ALTA) trial patients to determine the prognostic value of MMP-3. Plasma sample MMP-3 was measured by enzyme-linked immunosorbent assay. The primary outcome was the area under the receiver operating characteristic (AUROC) of MMP-3 at day 3 for the prediction of 90-day mortality. A total of 100 unique patient samples were evaluated and the AUROC analysis of day three MMP-3 showed an AUROC of 0.77 for the prediction of 90-day mortality (95% confidence interval: 0.67-0.87), corresponding to a sensitivity of 92% and specificity of 63% and an optimal cutoff value of 18.4 ng/mL. Patients in the high MMP-3 group (≥ 18.4 ng/mL) showed higher mortality compared to the non-elevated MMP-3 group (< 18.4 ng/mL) (47% vs. 4%, p < 0.001). A positive difference in day zero and day three MMP-3 concentration was predictive of mortality with an AUROC of 0.74 correlating to 73% sensitivity, 81% specificity, and an optimal cutoff value of + 9.5 ng/mL. Day three MMP-3 concentration and difference in day zero and three MMP-3 concentrations demonstrated acceptable AUROCs for predicting 90-day mortality with a cut-point of 18.4 ng/mL and + 9.5 ng/mL, respectively. These results suggest a prognostic role of MMP-3 in ARDS.


Effects of acute aerobic, resistance and combined exercises on 24-h glucose variability and skeletal muscle signalling responses in type 1 diabetics.
To compare the effect of high-intensity aerobic (AER), resistance (RES), and combined (COMB: RES + AER) exercise, on interstitial glucose (IG) variability and skeletal muscle signalling pathways in type 1 diabetes (T1D). T1D participants (6 M/6F) wore a flash glucose monitoring system in four randomized sessions: one control (CONT), and one AER, RES and COMB (40 min each). Mean amplitude of glycemic excursions (MAGE), standard deviation (SD) and coefficient variation (CV) of IG were used to compare the 24 h post-exercise IG variability. Blood and muscle samples were collected to compare exercise-induced systemic and muscle signalling responses related to metabolic, growth and inflammatory adaptations. Both RES and COMB decreased the 24 h MAGE compared to CONT; additionally, COMB decreased the 24 h SD and CV. In the 6-12 h post-exercise, all exercise modalities reduced the IG CV while SD decreased only after COMB. Both AER and COMB stimulated the PGC-1α mRNA expression and promoted the splicing of IGF-1Ea variant, while Akt and p38MAPK phosphorylation increased only after RES and COMB. Additionally, COMB enhanced eEF2 activation and RES increased myogenin and MRF4 mRNA expression. Blood lactate and glycerol levels and muscle IL-6, TNF-α, and MCP-1 mRNAs increased after all exercise sessions, while serum CK and LDH level did not change. COMB is more effective in reducing IG fluctuations compared to single-mode AER or RES exercise. Moreover, COMB simultaneously activates muscle signalling pathways involved in substrate metabolism and anabolic adaptations, which can help to improve glycaemic control and maintain muscle health in T1D.