Rasch Validation and Comparison of the Mini-BESTest and S-BESTest in Individuals With Stroke.
The purpose of this study was to compare the psychometric properties of the Mini-Balance Evaluation Systems Test (Mini-BESTest) and S-BESTest and to evaluate which is more suitable for use in clinical settings for individuals with stroke. This multicenter retrospective cross-sectional study investigated 115 individuals with stroke (mean age, 70.8 y [SD = 11.2 y]) who were able to stand without physical assistance. All individuals were examined with the BESTest and with the Mini-BESTest and S-BESTest scored based on the BESTest results. The data were analyzed using a Rasch analysis (partial credit model). The Mini-BESTest results revealed a correctly functioning rating scale, good fit of the data to the model (apart from 1 overfit item), good reliability for both persons and items (6 statistically detectable levels of balance ability), local dependence between 1 item pair, and essential unidimensionality. The S-BESTest results demonstrated disordered rating scale thresholds (1 response option required collapsing), good fit of the data to the model (apart from 1 underfit item), good reliability for both persons and items (5 statistically detectable levels of balance ability), local dependence between 2 item pairs, and essential unidimensionality. The analyses confirmed that the reliability of the S-BESTest was good and unidimensional and that the test provides several improved points, such as item redundancy and local independence of items. Nevertheless, the Mini-BESTest results supported previous findings as a whole and were better than those from the S-BESTest. Rasch analysis demonstrated that the Mini-BESTest was a better balance assessment scale than the S-BESTest for individuals with stroke based on its psychometric properties. The Mini-BESTest may serve as a useful scale for assessing balance in individuals with stroke, and a keyform plot and strata may help clinical decision-making in terms of interpreting scores and goal setting.


Nuclear pp64 is phosphorylated in both serine/threonine and tyrosine through complex pathways regulated by 12-O-tetradecanoylphorbol-13-acetate and platelet-derived growth factor.
Platelet-derived growth factor (PDGF) induces the time and dose dependent serine/threonine phosphorylation of pp64, a nuclear protein in normal rat kidney (NRK) cells. pp64 is phosphorylated additionally on tyrosine in SSV-transformed NRK cells. To further characterize the regulation of phosphorylation of pp64, other mitogens and inhibitors were studied. 12-O-tetradecanoylphorbol-13-acetate (TPA) but not epidermal growth factor (EGF) or insulin induced the phosphorylation of nuclear pp64. Addition of the inhibitor H7 to TPA-treated NRK cells resulted in a striking further increase in phosphorylation of pp64 and, to a lesser extent, in NRK cells treated with PDGF and H7. When cells were treated with PDGF and H7, pp64 was recognized by anti-phosphotyrosine antisera. The increased phosphorylation induced by H7 was inhibited when forskolin was included. This loss of phosphorylation in pp64 with forskolin treatment paralleled a loss of immunoreactivity of pp64 to anti-phosphosphotyrosine. Complex and independent pathways thus appear to signal the growth factor dependent nuclear phosphorylation of pp64, involving phosphorylations both on serine/threonine and on tyrosine.


Sleep and Epilepsy.
Seizures and antiepileptic drugs (AEDs) affect sleep macroarchitecture and may produce excessive daytime sleepiness (EDS) in patients with epilepsy. Sleep is a potent activator of seizures and epileptiform discharges. In some patients, seizures occur exclusively or predominately in sleep. Benign focal epilepsy of childhood with centrotemporal spikes (BECTS), supplementary sensorimotor area epilepsy (SSMA) and Lennox Gastaut syndrome are a few of the more common epilepsy syndromes characterized by nocturnal seizures. Excessive daytime sleepiness is a common complaint of patients with epilepsy. Causes of EDS include seizures, AEDs, poor sleep hygiene, and coexisting sleep disorders. Pharmacologic therapy is aimed at identifying the single most effective drug for a given seizure type or epilepsy syndrome. Polytherapy is associated with a higher likelihood of adverse effects--most notably, EDS. Poor sleep hygiene leads to sleep fragmentation that can exacerbate seizures and EDS. Primary sleep disorders should be suspected in patients with EDS, particularly those treated with monotherapy at low serum drug concentrations and well controlled seizures. Treatment of sleep disorders may lead to better seizure control.


Decreased prostaglandin-I2 stability in acute myocardial infarction.
It has been demonstrated that under certain conditions the in-vitro half-life of biologically active PGI2 in plasma is extremely shortened, which may result in-vivo in a local haemostatic imbalance. In 36 patients suffering from acute myocardial infarction a sequential change in in-vitro half-life of synthetic PGI2 was therefore studied during 3 weeks. 21 patients admitted turning out not to develop myocardial infarction served as follow-up controls. During and shortly after the acute episode the plasmatic half-life of PGI2 in-vitro was shortened by about 40%, improving continuously thereafter. No certain influence of either risk factors, sex or age could be discovered. A possible influence of various drugs administered in the hospital period has been excluded in 43 patients with proven coronary artery disease. No such changes occurred during acute angina pectoris attack in 12 patients. It remains to be established, whether the short-lasting destabilisation of PGI2 may be an acute disease-associated finding, or an important pathogenetic factor.


Clinicopathologic characteristics and outcomes of late onset lupus nephritis: a single centre experience.
Systemic Lupus Erythematosus (SLE) occurs in the reproductive age group. Renal involvement occurs less frequently in late-onset SLE than in reproductive-age SLE patients. Here, we aimed to study the clinical, serological and histopathological characteristics of late-onset lupus nephritis (LN). Late-onset LN was defined as disease onset after 47 years of age, corresponding to the average menopausal age. Records of biopsy proven late-onset lupus nephritis patients diagnosed between June 2000 and June 2020 were reviewed. Late-onset LN constituted 53 of 4420 patients (1.2%) biopsied during the study period. Females represented 90.65% of the cohort. Mean age of the cohort was 49.5 ± 7.05 years at the time of SLE diagnosis while its renal presentation was delayed by median duration of 10 months (IQR 3-48 months). Renal failure was present in 28 patients (52.8%) with acute kidney injury (AKI) (28.3%, n = 15) as the most common presentation. On histopathological analysis, class IV was observed in 23 patients (43.5%), crescents were observed in one-third cases and lupus vasculopathy in 4 patients (7.5%). All patients received steroids. Majority of patients (43.3%; n = 23) received Euro lupus protocol for induction. On median follow up duration of 82 months, renal flares were noted in 9 patients (17%) and 8 patients (15.1%) became dialysis dependent. Among 11 patients (21%) with infectious complications, 7 patients (13.2%) suffered from tuberculosis. Infections caused three-fourth of the deaths. Late-onset lupus nephritis is rare and presents as renal failure in majority. Renal biopsy affects the clinical decision of judicious use of immunosuppression which is imperative due to high rate of infections in this cohort.


Measuring Sexual Minority Stressors in Lesbian Women's Daily Lives: Initial Scale Development.
Lesbian women face unique sexual minority stressors (SMS) due to their stigmatized and marginalized status in society. Existing studies of SMS are primarily cross-sectional and use global measures of SMS. The goal of the present study was to develop a brief daily measure of SMS for use in daily diary or ecological momentary assessment (EMA) studies. Existing retrospective measures of SMS were reviewed, resulting in an initial pool of 29 items. Thirty-eight lesbian women (Mage=24.3 years, range: 19-30 years) completed a daily web-based survey including the SMS items for 12 days. Two response scales were tested; participants were randomized to receive a 3-point (for brevity) or 7-point (for precision) scale for the first 6 days and the other response scale for the remaining 6 days to counterbalance order. Findings suggest the 7-point scale was optimal because it provided greater variability. To reduce scale length, item correlations were examined to identify clusters and one item was retained from each cluster, reducing the scale to 18 items. Then, using HLM, null models with each item as the outcome were conducted to examine level-1 and level-2 variances; 8-, 10-, 12-, and 18-item scales were compared to identify the ideal number of items. The 8-item scale had the highest Cronbach's alpha (.85) and the smallest intraclass correlation (ICC; .13), suggesting these 8 items are optimal for capturing within-person variability in young lesbian women's daily SMS experiences. As researchers are increasingly interested in using EMA methods, this 8-item measure can assess SMS in lesbian women's everyday lives.


Association between oophorectomy and depression in patients with comorbidities: A nationwide cohort study in Taiwan.
This study investigated the long-term rates of depression after oophorectomy for benign gynecological conditions with or without comorbidities. This retrospective cohort study examined data from the National Health Insurance Research Database (NHIRD) involving 8199 women aged ≥20 years who underwent unilateral or bilateral oophorectomy for benign gynecological conditions (cases) between 2000 and 2013 (index date). A second cohort consisted of 32,796 women who did not undergo oophorectomy (controls) who were matched 4:1 to cases by age and index year. The follow-up time was more than 10 years. For all participants, the analysis accounted for comorbidities including hypertension, diabetes mellitus, hyperlipidemia, stroke, chronic obstructive pulmonary disease (COPD), chronic liver disease and cirrhosis, chronic kidney disease, and anxiety. Crude hazard ratios, adjusted hazard ratios, and 95% confidence intervals (CIs) were calculated according to multivariable Cox proportional hazard regression models adjusting for age, comorbidity, and the combination of oophorectomy with one comorbidity. Our results show that unilateral or bilateral oophorectomy, whether performed by laparotomy or laparoscopy, increases the overall risk of depression (aHR: 1.36, 95%CI: 1.19-1.55). Compared with controls, women aged <50 years had a significantly higher incidence of depression. Having diabetes (aHR: 1.66, 95%CI: 1.09-2.51), hypertension (aHR:1.56, 95%CI:1.14-2.14), hyperlipidemia (aHR: 1.46, 95%CI: 1.04-2.05), stroke (aHR: 1.91, 95%CI: 1.01-3.60), COPD (aHR: 2.06, 95%CI: 1.3-3.26), chronic liver cirrhosis (aHR: 1.99, 95%CI:1.52-2.61), or anxiety (aHR: 5.01, 95%CI: 3.74-6.70) increased higher risk of depression compared with not having these comorbidities after oophorectomy. The likelihood of depression was highest within the first 6 years following oophorectomy (3-5years:aHR:1.26, 95%CI:1.00-1.58). Oopherectomy increases the overall risk of depression. We offer useful information for surgical decision-making and preoperative assessments of women undergoing oophorectomy. It is concluded that a synergistic effect exists between oophorectomy and the comorbidities. Post-surgery, physicians should carefully evaluate the risk of depression developing amongst women with comorbidities. A postoperative follow-up time of at least 6 years is recommended, as this period was associated with a significantly higher rate of depression during our over 10-year follow-up.


CRISPR arrays as high-resolution markers to track microbial transmission during influenza infection.
Disruption of the microbial community in the respiratory tract due to infections, like influenza, could impact transmission of bacterial pathogens. Using samples from a household study, we determined whether metagenomic-type analyses of the microbiome provide the resolution necessary to track transmission of airway bacteria. Microbiome studies have shown that the microbial community across various body sites tends to be more similar between individuals who cohabit in the same household than between individuals from different households. We tested whether there was increased sharing of bacteria from the airways within households with influenza infections as compared to control households with no influenza. We obtained 221 respiratory samples that were collected from 54 individuals at 4 to 5 time points across 10 households, with and without influenza infection, in Managua, Nicaragua. From these samples, we generated metagenomic (whole genome shotgun sequencing) datasets to profile microbial taxonomy. Overall, specific bacteria and phages were differentially abundant between influenza positive households and control (no influenza infection) households, with bacteria like Rothia, and phages like Staphylococcus P68virus that were significantly enriched in the influenza-positive households. We identified CRISPR spacers detected in the metagenomic sequence reads and used these to track bacteria transmission within and across households. We observed a clear sharing of bacterial commensals and pathobionts, such as Rothia, Neisseria, and Prevotella, within and between households. However, due to the relatively small number of households in our study, we could not determine if there was a correlation between increased bacterial transmission and influenza infection. We observed that airway microbial composition differences across households were associated with what appeared to be different susceptibility to influenza infection. We also demonstrate that CRISPR spacers from the whole microbial community can be used as markers to study bacterial transmission between individuals. Although additional evidence is needed to study transmission of specific bacterial strains, we observed sharing of respiratory commensals and pathobionts within and across households. Video Abstract.


Neuroleptanalgesic drug combinations in the anaesthetic management of small laboratory animals.
Trials of different drug combinations for use in rabbits, guinea-pigs, rats, hamsters and mice are described in detail and experience over a 5-year period evaluated. Combinations of fentanyl citrate, fluanisone and diazepam provided exceptionally good anaesthesia in each species and were considered superior to other injectable agents.


Efficient gene-targeting in rat embryonic stem cells by CRISPR/Cas and generation of human kynurenine aminotransferase II (KAT II) knock-in rat.
The relative proportion of kynurenine aminotransferase (KAT) I-IV activities in the brain is similar between humans and rats. Moreover, KAT II is considered to be the main enzyme for kynurenic acid production in the brain. Taken together, human KAT II knock-in (hKAT II KI) rats will become a valuable tool for the evaluation of KAT II targeted drugs as a human mimetic model. Although we initially tried the approach by conventional gene-targeting via embryonic stem cells (ESCs) to generate them, we had to give up the production because of no recombinant ESCs. Accordingly, we developed a method to improve the efficiency of homologous recombination (HR) in ESCs by the combination with the CRISPR/Cas system. Co-electroporation of Cas9 plasmid, single guide RNA plasmid and hKAT II KI vector increased the number of drug-resistant colonies and greatly enhanced the HR efficiency from 0 to 36 %. All the clones which we obtained showed the same sequence as designed. These recombinant clones resulted in chimeras that transmitted the hKAT II KI allele to their offspring. hKAT II KI rats showed no reduction of KATs mRNA expression and the amount of kynurenic acid was similar between the hKAT II KI rats and the wild type in their brains. These results indicate that the methodology presented in this report can overcome the problem encountered in conventional gene-targeting that prevented production of humanized rats.


First Observation of the β3αp Decay of ^{13}O via β-Delayed Charged-Particle Spectroscopy.
The β-delayed proton decay of ^{13}O has previously been studied, but the direct observation of β-delayed 3αp decay has not been reported. Rare 3αp events from the decay of excited states in ^{13}N^{⋆} provide a sensitive probe of cluster configurations in ^{13}N. To measure the low-energy products following β-delayed 3αp decay, the Texas Active Target (TexAT) time projection chamber was employed using the one-at-a-time β-delayed charged-particle spectroscopy technique at the Cyclotron Institute, Texas A&M University. A total of 1.9×10^{5} ^{13}O implantations were made inside the TexAT time projection chamber. A total of 149 3αp events were observed, yielding a β-delayed 3αp branching ratio of 0.078(6)%. Four previously unknown α-decaying excited states were observed in ^{13}N at 11.3, 12.4, 13.1, and 13.7 MeV decaying via the 3α+p channel.


Agonist-dependent phosphorylation and nuclear dephosphorylation of glucocorticoid receptors in intact cells.
Phosphorylation and dephosphorylation has been suggested to influence the function of glucocorticoid receptors, but evidence for hormone-dependent changes in the phosphorylation state under physiological conditions is lacking. Here we show that in intact WEHI-7 mouse thymoma cells, labeled for 18-20 h with [32P]orthophosphate and [35S]methionine, glucocorticoids rapidly increase the average number of phosphates on the steroid-binding protein approximately from three to five. This stimulation is agonist-dependent since the antiglucocorticoid RU 486 (17 beta-hydroxy-11 beta,4-dimethylaminophenyl-17 alpha-propynyl estra-4,9-diene-3-one) has no effect by itself and blocks the cortisol-induced phosphorylation. Furthermore, the salt-unextractable nuclear bound receptors lose at least two phosphates compared to cytosolic and nuclear extractable forms. These results show for the first time that these hormone-dependent transcription regulators undergo agonist-induced phosphorylation and dephosphorylation which may affect their activity.


Bromelain immobilization in cellulose triacetate nanofiber membranes from sugarcane bagasse by electrospinning technique.
Cellulose triacetate (CTAB) synthesized by cellulose extracted from sugarcane bagasse, and commercial cellulose acetate (CA) were used to produce nanofiber membranes contained bromelain by electrospinning technique. About 1.3 g of cellulose acetate per gram of bagasse were obtained, and both CTAB and CA was characterized by analysis of Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The nanofiber membranes were produced by electrospinning process testing the following conditions: voltage 25 kV, flow rate 4 mL/h and distance 10 cm, using acetone/ dimethylformamide (DMF) (85:15 m/ m) to 15% cellulose triacetate (70% CA + 30% CTAB) or CA solutions. Scanning Electron Microscopy (SEM) was used to nanofiber membranes characterization. Bromelain was immobilized on the nanofiber membranes by crosslinking with glutaraldehyde and directly in the electrospinning step, the highest activity recovery was about 675% and in vitro controlled release tests were performed to semi-quantitatively evaluate the release of the enzyme bromelain thus demonstrating complete release process in 3 days.


Arthroscopic rotator interval closure: effect of sutures on glenohumeral motion and anterior-posterior translation.
The effect of arthroscopic rotator interval closure on glenohumeral motion and translation is not well understood, nor is the ideal location or number of sutures required for closure. The number of arthroscopic rotator interval closure sutures and their placement will have a significant effect on glenohumeral range of motion and anterior-posterior translation. Controlled laboratory study. Using a custom testing apparatus, the authors measured range of motion in 12 fresh-frozen cadaveric shoulders; anterior-posterior translation in adduction and neutral rotation was measured in 9. Specimens were initially tested without sutures and then tested after 3 interval closures using a random sequence of (1) an isolated medial suture at the level of the glenoid, (2) an isolated lateral suture 1 cm lateral to the glenoid, or (3) both sutures followed by removal of all sutures. Analysis of variance demonstrated that interval closure had a significant effect on decreasing flexion (mean, 6 degrees), external rotation (mean, 10 degrees), and anterior translation (mean, 3 mm) of the adducted shoulder. There was no significant difference between the 3 interval closures in any of the tests. Arthroscopic interval closure produced significant decreases in range of motion and anterior-posterior translation. The effects of single lateral or medial suture closures were similar to the use of 2 sutures. This study suggests that the initial effect of arthroscopic rotator interval closure on anterior translation of the shoulder will be similar whether 1 or 2 sutures are used. In vivo studies are necessary to determine if the effect of these 2 methods would be the same over time.


Helistat absorbable collagen hemostatic sponges in cutaneous surgery in HIV-1+ patients. Military Medical Consortium for the Advancement of Military Medicine (MMCAR).
While biopsies are often required for adequate diagnosis of skin lesions in HIV-1 infected patients, these procedures result in the possible exposure of medical personnel to blood and contaminated instruments. To reduce exposure of medical personnel to contaminated needles we have used collagen sponges instead of sutures to control bleeding from punch biopsy sites in HIV-1 infected patients. A collagen sponge was placed in all punch biopsy sites in HIV-1 infected patients. In cases where there was clinical evidence of local infection the sponges were removed 5-6 minutes after hemostasis was obtained. In over 500 biopsies in which Helistat collagen sponges were used, there have been no cases of secondary infection, and there have been no delays in healing. We believe that the use of these sponges provides a high degree of safety for the physician, which may assure that the commonly atypical clinical lesions seen in HIV-1 disease are biopsied. In addition, these sponges provide hemostasis, particularly significant in this patient population, and convenience, without a significant risk of secondary infection, and may provide some benefit in healing.


Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: a prospective, open-label, uncontrolled study.
The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients. The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function. This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day. Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients. CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).


[Cocaine-body-packing. Infrequent indication for laparotomy].
Body-packers or "mules" are drug smugglers who swallow cocaine-filled condoms in order to conceal them during air travel. Body pushers hide drug packages in the rectum or vagina. In a cooperative effort between the Frankfurt Airport Clinic and the GIZ-Nord (Goettingen University poison control center), we performed a retrospective study and developed an algorithm for the problem of "rupture of a cocaine-filled condom in a body-packer." In a retrospective analysis, the data of all cocaine body-packers and body pushers who were identified at Frankfurt International Airport from 1985 to 2001 were evaluated.Temporal development, demographic data, and surgical aspects were of special interest. From 1985 to 2001 a total of 280 body pushers and 2880 body-packers were identified: 63 "mules" (2.2%) developed symptoms of severe cocaine intoxication following rupture of a condom. Emergency laparotomy was performed on 20 patients (i.e., 32% of all symptomatic body-packers) and the condoms were removed, while 43 body-packers (68%) died before surgical therapy could be initiated. All operated patients survived. Severe cocaine intoxication is life threatening. Patients die from complications caused by generalized vasoconstriction. If the reason for severe cocaine intoxication is the rupture of a cocaine-filled condom,the only possible therapy consists of immediate laparotomy for removal of the condoms.


Modeling the Seasonal Variation of Windborne Transmission of Porcine Reproductive and Respiratory Syndrome Virus between Swine Farms.
Modeling the windborne transmission of aerosolized pathogens is challenging. We adapted an atmospheric dispersion model named the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model to simulate the windborne dispersion of porcine reproductive and respiratory syndrome virus (PRRSv) between swine farms and incorporated the findings into an outbreak investigation. The risk was estimated semi-quantitatively based on the cumulative daily deposition of windborne particles and the distance to the closest emitting farm with an ongoing outbreak. Five years of data (2014:2018) were used to study the seasonal differences of the deposition thresholds of the airborne particles containing PRRSv and to evaluate the model in relation to risk prediction and barn air filtration. When the 14-day cumulative deposition was considered, in winter, above-threshold particle depositions would reach up to 30 km from emitting farms with 84% of them being within 10 km. Long-distance pathogen transmission was highest in winter and fall, lower in spring, and least in summer. The model successfully replicated the observed seasonality of PRRSv, where fall and winter posed a higher risk for outbreaks. Reaching the humidity and temperature thresholds tolerated by the virus in spring and summer reduced the survival and infectivity of aerosols beyond 10-20 km. Within the data limitations of voluntary participation, when wind was assumed to be the sole route of PRRSv transmission, the predictive performance of the model was fair with >0.64 AUC. Barn air filtration was associated with fewer outbreaks, particularly when exposed to high levels of viral particles. This study confirms the usefulness of the HYSPLIT model as a tool when determining seasonal effects and distances and informs the near real-time risk of windborne PRRSv transmission that can be useful in future outbreak investigations and for implementing timely control measures.


Italian population data on thirteen short tandem repeat loci: HUMTH01, D21S11, D18S51, HUMVWFA31, HUMFIBRA, D8S1179, HUMTPOX, HUMCSF1PO, D16S539, D7S820, D13S317, D5S818, D3S1358.
A population study on thirteen short tandem repeat (STR) loci was performed on 223 unrelated Italian Caucasians. The DNA was amplified by PCR. Separation and detection of the amplified STR fragments was carried out by use of 377 automated system (Applied Biosystems Division/Perkin Elmer). All loci meet Hardy-Weinberg expectations, and the data show only five departures out of seventy-eight pairwise locus tests which is close to expectations of 5% (5/78 = 6.4%). When correcting for multiple tests, there is little evidence for departures from expectations between loci. The combined Power of Exclusion for the thirteen STR loci is 0.99999270. The results demonstrate that these loci will be very useful for human identification in forensic cases in Italy.


Prognostic value of early exercise testing after coronary stent implantation.
The clinical value of early exercise stress testing (EST) after coronary stenting to predict long-term clinical outcomes is unknown. Of 1,000 unselected patients who underwent coronary stenting, 446 random patients underwent early EST the day after intervention. Clinical long-term outcomes (41 +/- 20 months) were correlated with normal (n = 314 [70%]) or positive (n = 102 [23%]) EST results. Patients with inconclusive test results (n = 30 [7%]) were excluded from the analysis. Overall mortality was significantly higher in patients with positive EST results (9.3% vs 3.9%, p = 0.04). Major adverse cardiac events and cardiac mortality also tended to be higher in patients with positive stress test results (45.4% vs 35.4%, p = 0.08, and 4.1% vs 1.1%, p = 0.05, respectively). Patients with the combination of positive stress test results and incomplete revascularization appeared to be the group at highest risk for major adverse cardiac events (47.1% vs 33.3% for patients with normal stress test results and complete revascularization, p = NS). Negative stress test results reduced (odds ratio 0.329, 95% confidence interval 0.120 to 0.905, p = 0.031) and a lower ejection fraction increased (odds ratio 0.942, 95% confidence interval 0.897 to 0.989, p = 0.017) the risk for death. In conclusion, an early stress test after coronary stenting provides important prognostic information. Positive stress test results, especially in combination with incomplete revascularization, are associated with higher mortality, a trend toward more repeat revascularization procedures, and higher risk for major adverse cardiac events.


Effects of Lumbar Stiffness After Lumbar Fusion Surgery on Activities of Daily Living.
A retrospective cohort study. The aim of this study was to assess the effects of lumbar stiffness after lumbar fusion surgery on functional limitations, health-related quality of life, and activities of daily living (ADL). Postoperative outcomes after fusion surgery are usually assessed using patient-reported instruments to describe disability related to pain and health status. There are few studies on the effects of lumbar stiffness on ADL after lumbar fusion surgery. This study included 93 patients who underwent lumbar fusion surgery for degenerative lumbar disease. Their mean age was 69 years (range 51-79), and the mean follow-up was 34 months (24-46). The patients were categorized into 5 groups according to the number of segments involved: 0 level (decompression), 1 level, 2 levels, 3 levels, and 4 levels. They completed a 21-item questionnaire about their ADL and the Short Form Health Survey 36 (SF-36) to evaluate the effects of lumbar stiffness on ADL after surgery. There was a linear trend toward a decreased rating in all items in our questionnaire and in the physical component summary in the SF-36 related to postoperative lumbar stiffness. These trends were significantly related to the number of fused segments (P < 0.05 and P < 0.001, respectively). Patient satisfaction did not differ between the groups (P = 0.381). Patients who received a 1- or 2-level fusion reported no serious limitations in most ADL. Patients who received a 3- or 4-level fusion, especially 4-level fusion, reported more limitations because of postoperative lumbar stiffness. This study investigated in detail the effects of lumbar stiffness after fusion surgery on ADL. Spine surgeons should consider the patient's occupation and lifestyle in preoperative planning. These results will help the surgeon explain the possible outcomes to patients planning to undergo fusion surgery. 2.


Digital subtraction wrist arthrography: use of double contrast technique as a supplement to single contrast arthrography.
A new technique using double contrast after digital subtraction wrist arthrography is presented. Results of the double contrast wrist arthrograms were essential to the diagnosis, confirmed the diagnosis, or salvaged an otherwise poor or nondiagnostic examination. It was found that intra-articular injection of air augments the information obtained during postarthrogram active motion studies under fluoroscopy. Double contrast wrist arthrography has proved valuable when the standard contrast arthrogram fails to yield diagnostic information.


Symptom and demographic profiles in first-episode schizophrenia.
First-episode schizophrenia (FE-SZP) presents a diagnostic challenge because of symptomatic overlap between the various causes of psychosis. An early and accurate diagnosis is important for the implementation of appropriate treatment, for determining prognosis and for identifying research participants. In an effort to facilitate early diagnosis, we followed a group of first-episode psychosis patients with a presumptive diagnosis of schizophrenia who were subsequently diagnosed at 6-month follow-up with either schizophrenia (n=104) or other psychiatric diagnoses (n=19). The two groups-first-episode schizophrenia and first-episode non-schizophrenia-were compared on measures of demographics, symptoms, quality of life, premorbid adjustment and lateral dominance. Odds ratios were calculated for each variable and all significant variables were entered into a multivariate prediction model. The model showed that higher levels of anhedonia and hallucinations increased the odds of a final diagnosis of schizophrenia. This predictive model was validated in a smaller group of patients.


Stiff Composite Cylinders for Extremely Expandable Structures.
The realization of concurrently largely expandable and selectively rigid structures poses a fundamental challenge in modern engineering and materials research. Radially expanding structures in particular are known to require a high degree of deformability to achieve considerable dimension change, which restrains achievable stiffness in the direction of expanding motion. Mechanically hinged or plastically deformable wire-mesh structures and pressurized soft materials are known to achieve large expansion ratios, however often lack stiffness and require complex actuation. Cardiovascular or drug delivery implants are one example which can benefit from a largely expandable architecture that is simple in geometry and intrinsically stiff. Continuous shell cylinders offer a solution with these properties. However, no designs exist that achieve large expansion ratios in such shells when utilizing materials which can provide considerable stiffness. We introduce a new design paradigm for expanding continuous shells that overcomes intrinsic limitations such as poor deformability, insufficient stiffness and brittle behaviour by exploiting purely elastic deformation for self-expandable and ultra-thin polymer composite cylinders. By utilizing shell-foldability coupled with exploitation of elastic instabilities, we create continuous cylinders that can change their diameter by more than 2.5 times, which are stiff enough to stretch a confining vessel with their elastic energy. Based on folding experiments and analytical models we predict feasible radial expansion ratios, currently unmatched by comparable cylindrical structures. To emphasize the potential as a future concept for novel simple and durable expanding implants, we demonstrate the functionality on a to-scale prototype in packaging and expansion and predict feasible constellations of deployment environments.


High-performance liquid chromatographic determination of reproterol in plasma using on-line trace enrichment and amperometric detection with a rotating working electrode.
A method is described to determine nanogram quantities of reproterol in plasma. It consists of deproteinization of the plasma samples, on-line trace enrichment, and liquid chromatographic separation of the compounds brought on the analytical column, coupled with amperometric detection. Reliable quantitation can be done down to levels of 1 ng/ml.


Decapitation increases plasma sodium and potassium in the rat.
Sodium, potassium, and osmolality were measured in plasma obtained from conscious and decapitated rats. The sodium and potassium content of plasma derived from blood taken from decapitated rats via arterial cannulae or free-flowing trunk blood was significantly greater than that in conscious animals or animals killed by an overdose of pentobarbital. Plasma osmolality was not different. Hemoglobin was present in the plasma of decapitated rats, suggesting hemolysis. Hemolysis and subsequent release of intracellular potassium may be the cause of the elevated plasma potassium. The cause of the elevated sodium is unclear. This study points out the importance of considering the method of obtaining blood in determinations of plasma levels of biologic substances.


Sample Preparation Methods Following CellSearch Approach Compatible of Single-Cell Whole-Genome Amplification: An Overview.
Single cells are increasingly used to determine the heterogeneity of therapy targets in the genome during the course of a disease. The first challenge using single cells is to isolate these cells from the surrounding cells, especially when the targeted cells are rare. A number of techniques have been developed for this goal, each having specific limitations and possibilities. In this chapter, five of these techniques are discussed in the light of the isolation of circulating tumor cells (CTC) present at extremely low frequency in the blood of patients with metastatic cancer from the perspective of pre-enriched samples by means of CellSearch. The techniques described are micromanipulation, FACS, laser capture microdissection, DEPArray, and microfluidic solutions. All platforms are hampered with a low efficiency and differences in hands-on time and costs are the most important drivers for selection of the optimal platform.


Online whole-stage gait planning method for biped robots based on improved Variable Spring-Loaded Inverted Pendulum with Finite-sized Foot (VSLIP-FF) model.
Environmental adaptability and real-time control are significant to the actual application of biped robots. The current Spring-Loaded Inverted Pendulum (SLIP) walking exhibits the compliant interaction with environments. However, the movability and controllability of this model is limited owing to the lack of ankles. Moreover, complicated nonlinear optimization problems in gait generation bring difficulties to real-time control. To overcome these problems, this study proposes an online whole-stage gait planning method to enhance the bipedal walking performance. Firstly, considering the role of ankles, this study applies the proposed template model called Variable Spring-Loaded Inverted Pendulum with Finite-sized Foot (VSLIP-FF) model. Then a Finite State Machine (FSM)-based gait pattern including the corresponding bio-inspired gait strategies is established, which extends the single cyclic gait to the whole-stage gait. Secondly, to realize real-time gait planning, an online gait generator based on a neural network is applied to reduce the calculational burden. Finally, the method is applied on the simulation prototype and real robot platform for verification. Experimental results validate that the proposed method can achieve an autonomous gait with the online planning time of 0.01s, and the step length range is expanded by 37.52% compared with the traditional SLIP model.


Anthropogenic impact on long-term riverine CODMn, BOD, and nutrient flux variation in the Pearl River Delta.
In the Pearl River Delta (PRD), population growth and economic development have steadily increased the anthropogenic nutrient discharge into coastal waters. In this study, we employed the observed concentration and model reproduced runoff to quantify the interannual variation and the long-term (1985-2021) trends in riverine chemical oxygen demand (CODMn), biochemical oxygen demand (BOD), and nutrient fluxes. The annual CODMn and BOD fluxes increased slightly between 1999 and 2021. In comparison, the mean annual dissolved inorganic nitrogen (DIN) fluxes of the four eastern outlets increased significantly from 2.05 × 105 t/a in 1985-1995 to 3.11 × 105 t/a in 1999-2011 and then to 3.91 × 105 t/a in 2014-2021. The outlets with the largest contributions to the CODMn, BOD, and DIN fluxes were Humen and Modaomen, which are both located near large cities. By calculating the CODMn fluxes upstream of the PRD, we found that the CODMn fluxes from downstream in the PRD increased faster than the fluxes from upstream. It follows that the increase in CODMn at outlets was mostly driven by the contributions of downstream major cities. In addition, the proportion of ammonia nitrogen flux in the DIN flux decreased from over 50 % to under 10 % at most outlets. This indicates that the toxicity of DIN fluxes has been mitigated. The DIN fluxes also showed a positive correlation with surface chlorophyll a and a negative correlation with bottom dissolved oxygen outside the Pearl River Estuary (PRE). This implies that the changes in phytoplankton growth and oxygen levels outside the PRE are closely linked to the variation in river-delivered nutrients, and the increasing riverine nutrient input may result in the expansion of intensified low-oxygen conditions outside the PRE.


Psychometric evaluation of the Participation and Activity Inventory for Children and Youth (PAI-CY) 0-2 years with visual impairment.
To identify and monitor the developmental and participation needs of visually impaired (VI) children, the Participation and Activity Inventory for Children and Youth (PAI-CY) has recently been developed involving end-users as stakeholders. The aim was to investigate psychometric properties of the PAI-CY for children between 0 and 2 years. Responses from 115 parents were included in item analyses, after which a combination of classical test theory and item response theory (IRT) was used. Internal consistency, known-group validity, and test-retest reliability at item and scale level were investigated. After deleting four items, the PAI-CY met IRT assumptions, i.e., unidimensionality, local independence, and monotonicity, and satisfactory model fit was obtained. Participants with more severe VI and comorbidity scored significantly worse than those with less severe VI and without comorbidity, supporting known-group validity. Satisfactory internal consistency and test-retest reliability were obtained (Cronbach's alpha 0.95, kappa 0.60-0.91, ICC 0.920). The PAI-CY 0-2 years has acceptable psychometric properties and can be used to systematically assess and monitor developmental and participation needs of very young children with VI from parents' perspectives in low vision practice and research. Confirmation of psychometric properties is necessary, possibly facilitating further item reduction, increased precision, and improved user-friendliness.


History-adjusted marginal structural analysis of the association between hemoglobin variability and mortality among chronic hemodialysis patients.
Hemoglobin variability is common among dialysis patients, and has been associated with increased mortality. The causal nature of this association has been difficult to ascertain because of potential time-dependent confounding, for which traditional statistical methods do not control. A retrospective cohort of 34,963 Fresenius Medical care dialysis patients from 1996 was assembled. Hemoglobin variability, absolute hemoglobin level, and temporal hemoglobin trend were measured over rolling 6-mo exposure windows. Their association with mortality was estimated using history-adjusted marginal structural analysis that adjusts for time-dependent confounding by applying weights to observations inversely related to the predictability of observed levels of hemoglobin. In the primary analysis, each g/dl increase in hemoglobin variability was associated with an adjusted hazard ratio (HR) [95% confidence interval (CI)] for all-cause mortality of 1.93 (1.20 to 3.10). Neither higher absolute hemoglobin level nor increasing hemoglobin trend were significantly associated with mortality; adjusted HR (95% CI) 0.85 (0.64 to 1.11) and 0.60 (0.25 to 1.45), respectively. Marginal structural analysis demonstrates that hemoglobin variability is associated with increased mortality among chronic hemodialysis patients, and that this effect is more pronounced than appreciated using standard statistical techniques that do not take time-dependent confounding into account.


Association of Copeptin With Sense of Coherence in Individuals With Varying Degrees of Glucose Intolerance.
This study aimed to examine the association of serum copeptin levels, a surrogate marker of arginine-vasopressin secretion with sense of coherence (SOC) among individuals with varying degrees of glucose intolerance. The study was conducted in 120 age- and sex-matched individuals who were divided equally into three groups. Group A included individuals with normal glucose tolerance; group B, individuals with prediabetes (impaired glucose tolerance and/or impaired fasting glucose); and group C, individuals with newly detected diabetes mellitus (NDDM). SOC, perceived stress scale (PSS), copeptin, anthropometry, glycated hemoglobin, insulin, and salivary cortisol were measured in all study participants. The SOC score was found to be significantly lower in group C compared with group A (p < .001) and group B (p = .006). The PSS score was found to be significantly higher in group C compared with group A (p = .002). No significant difference was found between PSS scores of groups B and C (p = .25). Copeptin levels were found to be significantly higher in group C compared with group A (p = .016). Copeptin levels in group C did not differ significantly from those in group B (p = .056). There was a significant negative correlation between serum copeptin levels and SOC in the NDDM group C (r = 0.31, p = .048) and overall (r = 0.19, p = .037). In multiple regression analysis, SOC emerged as the variable with the strongest association with 2-hour postprandial plasma glucose and glycated hemoglobin. Individuals with NDDM displayed significantly higher serum copeptin levels that inversely correlated with SOC, a global measure of stress coping ability.


The beneficial effect of early and prolonged kangaroo mother care on long-term neuro-developmental outcomes in low birth neonates - A cohort study.
Kangaroo mother care (KMC) has immense short-term benefits, but data on long-term outcomes are scarce. Hence, this study aimed to compare the neurodevelopmental outcomes at 12 months of corrected age (CA) in infants <2000 g receiving early and prolonged KMC to a control group. This was a cohort study that was conducted from January 2017 to November 2018. All neonates<2000 g were eligible for the study. Neonates that received early initiation (<72 h of life) and prolonged KMC comprised the intervention group and were compared to neonates without the intervention. Bayley Scales of Infant and Toddler Development, Third edition (BSID-III) was done at 12 months of CA, and this was analysed using t-test and multi-linear regression analysis. There were 75 neonates in the intervention and 69 in the control group. Baseline characteristics were comparable. We found higher composite scores for cognition (110.38 ± 9.89 vs. 105.44 ± 8.77, p value = 0.023), language (107.51 ± 10.72 vs. 101.05 ± 12.06, p value = 0.014) and adaptive behaviour (87.97 ± 9.97 vs. 80 ± 9.1, p value<0.001) in the early and prolonged KMC group in comparison to the control group. Infants with early and prolonged KMC have better neurodevelopmental outcomes in terms of cognition, language and adaptive behaviour at 12 months of CA.


Effect of human prolactin administration on gonadotropin and thyrotropin secretion in normal men.
To test the hypothesis that PRL is able to feedback negatively on its own secretion (short-loop feedback) in humans via augmentation of the turnover of tuberoinfundibular dopamine (TIDA), the effects of the administration of purified hPRL on endogenous LH, FSH and TSH were assessed. Purified hPRL, given in an i.v. loading dose of 90 micrograms followed by a continuous infusion of 1.39 micrograms/min to 4 normal male volunteers resulted in a tripling of PRL levels (10.5 +/- 1.9 micrograms/L increasing to 30.9 +/- 3.6 micrograms/L) at the end of 90 min. There were no changes in LH, FSH or TSH levels, however, during or following the infusion. Purified hPRL was also given in 1 and 8 micrograms/kg doses IM to 5 normal male volunteers. Although PRL levels did not rise significantly with the 1 microgram/kg dose, levels almost doubled with the 8 micrograms/kg dose (9.5 +/- 2.2 micrograms/L increasing to 17.4 +/- 1.5 micrograms/L). Again, LH, FSH and TSH levels did not change significantly over the three hour period of sampling with either dose. In conclusion, in this study we found that a 2-3 fold increase of circulating PRL levels maintained for 1.5-3 h exerted no apparent effects on the secretion of endogenous LH, FSH and TSH. This study provides direct evidence against the existence of a short-loop feedback occurring via TIDA activation in humans over this time interval but does not rule out the possibility that such feedback may occur with more prolonged states of hyperprolactinemia or via other mechanisms or the possibility of an effect on the hypothalamic pulse generator.


Assessment of anesthesia machine redesign on cleaning of the anesthesia machine using surface disinfection wipes.
The use of surface disinfection wipes after induction of anesthesia improves anesthesia machine cleaning. We assessed whether anesthesia machine surface redesign improves disinfection wipe cleaning by anesthesia residents. Sixteen anesthesia residents were assigned to 2 cases in series. The first case was randomly assigned to regional knee or hip surgery, a brief or detailed checklist, and the Perseus A500 (redesigned) or GE Aespire 7900 (conventional) machine. The second case was assigned to the opposite for each condition. Setup checklists included cleaning instructions. Eight machine sites representing redesign were contaminated with fluorescent gel prior to setup and reassessed after setup to assess cleaning efficacy. Cleaning was compared by fluorescence quantification of before and after setup images. Our primary hypothesis was that, overall, more sites would be cleaned on the Perseus machine. Our secondary hypothesis was that redesign would affect some sites. Overall, the number of sites cleaned did not differ between machines (median 0.74 more sites out of 8 for the Perseus A500; 25th and 75th percentiles, -0.34 and 1.04; P = .093). However, greater cleaning was observed for the work surface and manual bag arm/hose of the Perseus machine (0.58 more sites out of 2; 25th and 75th percentiles, 0.35 and 1.05; P = .0004). The number of sites cleaned overall did not differ between the conventional and redesigned Perseus A500 machines. However, the redesigned work surface and smooth manual bag arm features improved resident cleaning with surface disinfection wipes.


Biosynthesis of Au nanoparticles supported on Fe3O4@polyaniline as a heterogeneous and reusable magnetic nanocatalyst for reduction of the azo dyes at ambient temperature.
In this research Au nanoparticles, supported on Fe3O4@polyaniline as a magnetic nanocatalyst, was synthesized and its performance has been evaluated to reduce Methylene Blue (MB) and Methyl Orange (MO) from aqueous solutions. Gold nanoparticles, as a nanocatalyst with excellent activity, were prepared through the reduction of Au3+ using a wild herbal extract (Allium Sp) without any toxic chemical compounds and harmful materials. The synthesized Fe3O4@PANI-Au magnetic nanocatalyst was characterized by different instruments. To investigate the effect of nanocatalyst concentration on the degradation rate of azo dyes, two different catalyst concentrations were used at ambient temperature. According to the carried out calculations, degradation reaction of azo dyes with NaBH4 in presence of the nanocatalyst is 103 to 104 times faster than degradation without using the catalyst.


Chloroquine, hydroxychloroquine, and COVID-19: Systematic review and narrative synthesis of efficacy and safety.
The COVID-19 pandemic has required clinicians to urgently identify new treatment options or the re-purposing of existing drugs. Of particular interest are chloroquine (CQ) and hydroxychloroquine (HCQ). The aims of this systematic review are to systematically identify and collate 24 studies describing the use of CQ and HCQ in human clinical trials and to provide a detailed synthesis of evidence of its efficacy and safety. Of clinical trials, 100% showed no significant difference in the probability of viral transmission or clearance in prophylaxis or therapy, respectively, compared to the control group. Among observational studies employing an endpoint specific to efficacy, 58% concurred with the finding of no significant difference in the attainment of outcomes. Three-fifths of clinical trials and half of observational studies examining an indicator unique to drug safety discovered a higher probability of adverse events in those treated patients suspected of, and diagnosed with, COVID-19. Of the total papers focusing on cardiac side-effects, 44% found a greater incidence of QTc prolongation and/or arrhythmias, 44% found no evidence of a significant difference, and 11% mixed results. The strongest available evidence points towards the inefficacy of CQ and HCQ in prophylaxis or in the treatment of hospitalised COVID-19 patients.


Pathology and prognosis of persistent stable pure ground-glass opacity nodules after surgical resection.
This study aimed to show the pathologic results of pure ground glass opacities (pGGOs) that showed no change in patients who underwent surgical resection. The data used in this study were collected from the records of patients who underwent surgical resection for pGGOs between January 2004 and December 2009. All pGGOs were detected and followed up until operation with high-resolution computed tomography at our hospital and were followed up by computed tomography of the chest at least 2 years after operation. Surgical resection was performed for patients with pGGOs if no change was observed after a minimum of 1 month of follow-up and if any growth of the nodules or newly formed solid components occurred in pGGOs of any size. Forty-six patients were enrolled into the study group. No changes in the pGGOs during serial follow-up occurred in 39 patients (84.8%), and 7 patients (15.2%) underwent surgical resection because of growth of the lesions or newly developed solid lesions during follow-up. Of 39 patients in the no-change group, pathologic types of the cancerous pGGOs in 23 patients included adenocarcinoma in situ in 21 patients, minimally invasive adenocarcinoma in 1 patient, and invasive adenocarcinoma in 1 patient. In the change group, 5 patients were diagnosed with cancer. Between the two groups, there was no difference in sex, time intervals, or tumor size. Neither group had lymph node metastasis or recurrence. This study showed the pathology of persistent stable pGGO postoperatively, which confirmed the 59% chance of a cancer diagnosis including adenocarcinoma in situ, minimally invasive adenocarcinoma, or invasive adenocarcinoma.


Effect of obesity and insulin on immunity in non-insulin-dependent diabetes mellitus.
To understand the effect of obesity and insulin on immune functions in non-insulin-dependent diabetes mellitus (NIDDM). Fourteen obese NIDDM (body mass index (BMI)=30.6+/-1.1), seven non-obese NIDDM (BMI=24.2+/-0.5) and five obese non-NIDDM (BMI=28.3+/-0.67). We first examined the influence of insulin on the proliferation of several human cell lines. Second, we compared several immune functions between obese and non-obese NIDDM, and obese non-NIDDM patients using peripheral blood mononuclear cells. Insulin decreased proliferation of T-cell lines but not that of other types of cell lines. Furthermore, obesity augmented the production of IL-1beta which could have cytotoxity against islet beta cells in NIDDM. Our data suggested that the pathophysiology of NIDDM could be affected by the change of immunity due to obesity, and the treatment of obesity in NIDDM may be important from an immunological aspect.


Percutaneous aspiration biopsy of malignant lung lesions using the Chiba needle. An initial experience.
The fine gauge Chiba needle was evaluated in percutaneous aspiration biopsy in 20 patients with suspected malignant lung neoplasm. Adequate aspirate can be obtained with one biopsy. A confident cytological diagnosis of malignancy was made in 19 out of 20 patients. Most of the patients were elderly. Nine patients developed pneumothoraces which were small and asymptomatic. The needle is easy to handle and very acceptable to patients. This needle therefore appears to be very suitable for percutaneous aspiration biopsy of lung neoplasms and possibly other non-neoplastic lesions too. It promises to supersede the larger aspiration needles currently in use.


Real-time tissue elastography assessment of skin and subcutaneous tissue strains in legs with lymphedema.
To confirm the feasibility of assessing strains of the skin and subcutaneous tissue in normal legs and legs with lymphedema via free-hand real-time tissue elastography (RTE) using a phantom. After placing a phantom on the skin, we measured the strains of the phantom (S p), skin (S sk), and subcutaneous tissue (S sc) of the inner thigh and calf by free-hand RTE in 35 healthy volunteers. A reference S p was set using these data. We then assessed S sk and S sc in each leg of 15 patients with unilateral stage II lymphedema. In the healthy volunteers, the strain was largest in the subcutaneous tissue of the thigh, followed by the subcutaneous tissue of the calf, skin of the thigh, and skin of the calf. These differences were each significant. In the patients with unilateral lymphedema, S sk and S sc in the thigh and calf were not different between the affected and unaffected legs. It was feasible to assess the strains of the skin and subcutaneous tissue using free-hand RTE and standardization of the compression force using a phantom. We failed to demonstrate decreased strains of the skin and subcutaneous tissue in legs with stage II lymphedema compared with healthy legs.


[Examination of the acute effect of prednisolone on the acid secretion of the stimulated gastric mucosa in man].
In comparison with the maximal acid stimulation produced by intravenous infusion of histalog (2 mg/kg bw/h), a single intravenous injection of 25 mg prednisolone during maximal acid stimulation produced by pentagastrin (1.5 mug/kg bw/h) does not cause a significant change of secretion rate or ionic composition of gastric juice in man. This suggests that there is a greater dependence of histalog stimulation than of pentagastrin stimulation on the normal secretion of glucocorticoids.


Determination of the absolute stereochemistry of chiral biphenanthryls in solution phase using chiroptical spectroscopic methods: 2,2'-Diphenyl-[3,3'-biphenanthrene]-4,4'-diol.
Although the exciton coupling model has been widely used in the literature to suggest the absolute configuration using electronic circular dichroism (ECD) spectra, chiral biphenanthryl systems are one group of molecules where the application of the exciton model yields ambiguous conclusions. The use of 2,2'-diphenyl-[3,3'-biphenanthrene]-4,4'-diol, known as VAPOL, as a chiral ligand for enantioselective catalysis necessitates the reliable determination of its absolute configuration. Based on the X-ray diffraction data of its phosphoric amide derivative, the configuration of VAPOL has been determined in the literature to be (+)-(aS). The experimental vibrational circular dichroism, ECD and optical rotatory dispersion spectra, and corresponding quantum mechanical predictions of VAPOL are used in this manuscript to independently determine its absolute configuration.


Liquid chromatography-tandem mass spectrometry for the identification of impurities in d-allethrin samples.
A previous GC/MS study highlighting the impurity profile of the synthetic pesticide d-allethrin is extended here to validate and confirm the impurities identity through the development of soft ionisation HPLC-MS methods. To accomplish this, we developed a reverse phase LC-MS analysis in gradient elution with two distinct soft ionisation techniques, the atmospheric pressure ionisation with electrospray source (API-ESI) and the chemical ionisation (APCI). A single quadrupole and an ion trap, which allowed the simultaneous determination of the molecular masses and structural information of the impurities by acquisition of collisionally induced (CID) product ions spectrum and in-source fragmentation, were employed as analysers. Single quadrupole and ion trap analysers resulted perfectly matching in the d-allethrin impurity fragmentation patterns. All the main impurities over 0.1% identified by GC/MS were confirmed. Results indicate that the proposed HPLC/MS method was found appropriate to confirm the presence of impurities such as chrysolactone, chloro allethrin derivatives, allethrolone and chrysanthemic acid, excluding their formation under GC/MS strong ionisation condition.


Inhibition of Tau amyloid fibril formation by folic acid: In-vitro and theoretical studies.
Tauopathy belongs to a various class of neurodegenerative diseases in which insoluble Tau aggregates are formed, and cellular function is lost, leading to neuronal death. Various therapeutic strategies have been investigated, and many drugs have been proposed as a cure for these diseases but their toxicity and adverse side effects, limit their consumption by humans. Alternatively, the use of non-toxic medicine without any adverse or undesirable secondary effects like nutrients, vitamins, as well as herbal and mineral supplements is common and continues to increase each year. Folic acid is a form of vitamin B and plays a vital role in the synthesis of nucleic acid, methionine regeneration, and in shuttling one-carbon units essential for normal cell division and growth. We investigated the interaction between folic acid and Tau protein, then experimental and theoretical evidence were provided for the suppressing effects of folic acid on Tau fibril formation. The obtained results showed that folic acid could interact with Tau through a spontaneous binding process, mainly by hydrophobic forces, and this interaction leads to a decline in protein-protein interactions through stabilizing its native state, limiting successful Tau-seed oligomerization and consequently decelerating polymerization of Tau amyloid aggregates.


GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity.
Pediatric cancers often mimic fetal tissues and express proteins normally silenced postnatally that could serve as immune targets. We developed T cells expressing chimeric antigen receptors (CARs) targeting glypican-2 (GPC2), a fetal antigen expressed on neuroblastoma (NB) and several other solid tumors. CARs engineered using standard designs control NBs with transgenic GPC2 overexpression, but not those expressing clinically relevant GPC2 site density (∼5,000 molecules/cell, range 1-6 × 103). Iterative engineering of transmembrane (TM) and co-stimulatory domains plus overexpression of c-Jun lowered the GPC2-CAR antigen density threshold, enabling potent and durable eradication of NBs expressing clinically relevant GPC2 antigen density, without toxicity. These studies highlight the critical interplay between CAR design and antigen density threshold, demonstrate potent efficacy and safety of a lead GPC2-CAR candidate suitable for clinical testing, and credential oncofetal antigens as a promising class of targets for CAR T cell therapy of solid tumors.


Simple method for measuring center of mass work during field running.
The purpose of this study was to propose and validate a new simple method for calculation of center of mass work during field running, in order to avoid the use of costly and inconvenient measurement devices. This method relies on spring-mass model and measurements of average horizontal velocity, and contact and flight times during running. Ten male, recreational subjects ran on a dynamometer treadmill at different velocities ranging from 2.22 to 4.44 m·s-1 during 4 min 30 s for each velocity. Twenty consecutive steps were analyzed after 3 min 30 s. The potential (Wpot), forward kinetic (Wkinf) and the total center of mass (Wext) work data obtained with this new method were compared with the reference data calculated from ground reaction force measurements. Wext, Wpot and Wkinf values calculated with the proposed method were respectively +3.39 ± 0.77% higher, -4.14 ± 0.72% lower and +7.34 ± 1.08% higher than values obtained by the reference method. Furthermore, significant linear regressions close to the identity line were obtained between the reference and the proposed method values of works (r = 0.99, p < 0.05 for Wext; r = 0.98, p < 0.05 for Wpot; r = 0.98, p < 0.05 for Wkinf). It was concluded that this new method could provide a good estimate of center of mass work in field running thanks to a few simple mechanical parameters.


Medical renal diseases are frequent but often unrecognized in adult autopsies.
Kidney diseases affect many hospitalized patients and contribute to morbidity and mortality. Therefore, kidney disease should be prevalent, but the frequency and spectrum of medical renal pathology in autopsy specimens has not been well documented. We sought to determine the spectrum of medical renal pathology in adult autopsy specimens and the frequency of overlooked diagnoses. We reviewed the hematoxylin- and eosin-stained kidney sections from 140 adult autopsies performed at a large teaching hospital over a 2-year period. Fifty-eight cases (41%) had findings warranting further analysis, including alterations in glomerular matrix and/or cellularity, atypical or pigmented casts, thrombi, tubulointerstitial or vascular inflammation, or deposition of amorphous material. After additional studies and clinical correlation, the pathologic changes in 43 cases (31%) were categorized as follows: diabetic nephropathy, bile cast nephropathy, thrombotic microangiopathy, infection-related glomerulonephritis, focal necrotizing/crescentic glomerulonephritis, oxalate nephropathy, light-chain cast nephropathy, amyloidosis, urate nephropathy, hemosiderosis, antineutrophil cytoplasmic antibody-associated vasculitis, polyoma virus nephropathy, atheroembolic disease, and nephrocalcinosis. These diagnoses were not reported in 26 (60%) cases during the initial autopsy evaluation. This study demonstrates that medical renal diseases are common in autopsy cases, but significant diagnoses can be easily overlooked. Autopsy kidney specimens are a rich source of renal pathology and their evaluation should be emphasized in anatomic pathology residency training. Ultimately, our understanding of how kidney disease contributes to morbidity and mortality will benefit from accurate recognition of renal pathology in autopsy specimens.


Regional distribution of rabies viral antigen in central nervous system of human encephalitic and paralytic rabies.
We studied the distribution of rabies viral antigen in the brain and spinal cord of 7 patients with rabies by immunohistochemical techniques. Four patients presented with encephalitis, the remaining 3 had paralysis. Neither the rabies viral antigen distribution nor inflammation paralleled clinical presentations. Patients who had survival times of 7 days or less (4/7) had a greater amount of antigen-positive neurons in brainstem and spinal cord regardless of the clinical type. Neuroglial cells were also found to contain rabies antigen. Our findings suggest that virus localization may not account for the difference in clinical manifestations.


Benefit of crizotinib in a lung cancer patient with discordant ALK testing results.
Crizotinib is a first line treatment for patients with non-small cell lung cancer (NSCLC) harboring translocations in anaplastic lymphoma kinase (ALK). The current gold standard for determining ALK status is fluorescence in-situ hybridisation (FISH), but immunohistochemistry (IHC) is becoming increasingly popular due to lower cost. There are currently few reports on clinical outcomes with crizotinib therapy in patients who have tested negative by FISH and positive by IHC. A 53 year old lifelong non-smoking, physically active male with newly diagnosed Stage IV NSCLC presented with shortness of breath on exertion one month prior to referral. Staging CT scan failed to show a discreet lung lesion, but the left lower lobe was collapsed due to pleural effusion. Pleural fluid showed adenocarcinoma and IHC was positive for an ALK mutation, while FISH was negative. Pre-treatment PET-CT showed hypermetabolic, enlarged lymph nodes in the mediastinum and retroperitoneum. Partially due to patient concerns about cytotoxic chemotherapy toxicity, crizotinib therapy was instituted. Repeat CT conducted two months after crizotinib initiation showed a decrease in lymphadenopathy at all sites compared to the PET-CT. Furthermore, the patient showed clinical improvement, with less drainage through his PleurX catheter and stability of his excellent performance status. After 12 months on crizotinib CT showed ongoing improvement in lymphadenopathy. His bloodwork has been stable, and he denies significant drug toxicity. This case illustrates a sustained response to crizotinib therapy in a patient with an ALK translocation identified by IHC, but with negative FISH testing. The literature suggests that the population with these discordant results could be up to 19% of ALK positive NSCLC. Patients in this subgroup who are receiving crizotinib should be identified and outcome data pooled. However, in the interim, oncologists may wish to consider targeted therapy for these discordant patients.


Studies on the trigeminal antidromic vasodilatation and plasma extravasation in the rat.
Antidromic stimulation of sensory peripheral branches of the trigeminal system (mental nerve) led to cutaneous vasodilatation and increased vascular permeability in rats anaesthetized with urethane. The antidromic vasodilatation observed in intact animals was not altered by decentralization or sympathectomy. Both antidromic vasodilatation and neurogenic plasma extravasation remained unaffected by pre-treatment with cimetidine, indomethacin, baclofen, guanethidine plus phentolamine and propranolol, but were significantly reduced by cimetidine plus mepyramine and atropine, suggesting that cholinergic and histaminergic components might be involved in the sensory neurogenic responses. Methysergide reduced only the extravasation, suggesting that probably serotonin liberated by mast cells upon sensory stimulation can contribute to the neurogenic responses. In tests using substance P (SP) antagonists (D-pro4, D- trp 7, 9, 10)-SP (4-11) and (D-pro2, D-trp 7, 9)-SP it was found that they are more active in reducing the neurogenic extravasation than the vasodilatation. In addition it was observed that (D-pro 4, D-trp 7, 9, 10)-SP (4-11) was the most potent substance P antagonist in reducing the plasma extravasation and antidromic vasodilatation resulting from sensory stimulation.


Dual effect of erbB-2 depletion on the regulation of DNA repair and cell cycle mechanisms in non-small cell lung cancer cells.
Overexpression of the erbB-2 tyrosine kinase receptor, p185erbB-2, is a common alteration in non-small cell lung cancer (NSCLC) and has been associated with poor prognosis and a tumor drug resistance phenotype. In this study, we have examined the consequences of erbB-2 depletion on DNA repair, cell cycle, and apoptosis using a panel of NSCLC cell lines constitutively overexpressing erbB-2 receptor. Depletion of the erbB-2 was achieved using the tyrosine kinase inhibitor CP127,374 which promotes erbB-2 degradation. Treatment with CP127,374 concentrations which deplete erbB-2 and inhibit tyrosine phosphorylation resulted in downregulation of DNA repair mechanisms and cell accumulation at G1 phase of the cell cycle. GI arrest was observed in cells with mutated p53 as well as cells lacking p53 protein, suggesting a p53-independent mechanisms. NSCLC cells which overexpress erbB-2 were more resistant to cisplatin-induced cytotoxicity in comparison to cells expressing low levels of erbB-2. Treatment with CP127,374 alone did not result in any induction of apoptosis. A combination of CP127,374 and cisplatin, however, was more potent in cell growth inhibition and induction of apoptosis compared to treatment with cisplatin alone. Together, our results further support a pivotal role of erbB-2 signaling in the regulatory balance between DNA repair, cell cycle checkpoints and apoptosis; all these mechanisms are essential determinants for tumor cell destiny following chemotherapy stress.


Second Percutaneous Transluminal Angioplasty Versus Surgical Reconstruction for Hemodialysis Access Failure Within a Short Time Period.
The purpose of this study was to compare patency and nonabandonment rates for second percutaneous transluminal angioplasty (PTA) and surgical reconstruction for the treatment of failing vascular access due to restenosis or reocclusion in a short time after initial PTA. Seventy two consecutive patients who underwent second treatment within 90 days after the initial PTA were evaluated retrospectively. The patency (time to corrective procedure) and access abandonment were compared among patients who underwent a second PTA (n = 35) and those who underwent surgical reconstruction (n = 37). Univariate and multivariate analyses were performed to determine independent predictors of patency and access abandonment at 1 year after the treatment. At 1 year after the treatment, the patency rates were 35.1% and 11.4% (P = 0.02) and nonabandonment rates were 64.9% and 77.1% (P = 0.25) for surgical reconstruction and second PTA, respectively. The Kaplan-Meier survival analysis showed that the surgical reconstruction group had better patency probability (P = 0.02), but there was no difference in the nonabandonment probability between the groups (P = 0.29). Shorter time to retreatment was associated with good patency. The female gender was likely to be associated with access abandonment. The access abandonment between the 2 procedures had no difference, although surgical reconstruction provided better patency than second PTA.


Arterial hypertension and female sexual dysfunction in postmenopausal women.
To evaluate female sexual dysfunction in hypertensive postmenopausal women and the effects of antihypertensive therapy. Female sexual dysfunction was assessed by the Female Sexual Function Index (FSFI) in three groups of postmenopausal patients: normotensive women (group A: 240 women), hypertensive women without therapy (group B: 220 women), hypertensive women on therapy (group C: 80 women). The incidence of female sexual dysfunction was increased in group B compared to groups A and C. Healthy patients showed higher FSFI scores compared to hypertensive patients (groups B and C). Hypertensive-treated patients accounted for higher scores in all items compared to hypertensive patients without therapy. Essential hypertension significantly affects female sexual function. Physicians should recognize and properly manage FSD in hypertensive women.


A comprehensive overview of tumour deposits in colorectal cancer: Towards a next TNM classification.
The management of colorectal cancer (CRC) highly relies on the TNM staging system. Tumour deposits (TDs), important histoprognostic factors, are detected in approximately 20% of CRCs and associated with poor prognosis. Integration of TDs in the TNM staging remains a subject of lively debate and differs over the successive TNM classifications. Currently TDs, whatever their number, are considered in pathologic staging only in the absence of lymph node metastasis (LNM; subcategory pN1c). However, the medical community is divided over this way of integrating TDs in the TNM staging system. Considering the personalization of the type and duration of adjuvant chemotherapy in stage III colon cancer according to the number of LNM, this issue has become of growing importance. Thus, ignoring TDs in the presence of LNM represents a major prognostic underestimation and leads to wrong therapeutic decisions. Hence, considering the growing significance of prognostic role, the scientific complexity, and a potential therapeutic effect of TDs, we provide an overview of current knowledge about TDs. Based on the results from recent publications, we also provide plausible scenarios of integration of TDs into the next TNM classification system.


Soluble receptor for advanced glycation end products and increased aortic stiffness in the general population.
It has been suggested that accumulation of advanced glycation end products (AGEs) is involved in several pathophysiological processes in the vessel wall. We hypothesized that low levels of the soluble receptor for AGEs (sRAGE) might be associated with increased arterial stiffness, a manifestation of vascular ageing in the general population. Using a cross-sectional design, we analyzed 1077 subjects from the Czech post-MONICA study. The aortic pulse wave velocity (aPWV) was measured using a Sphygmocor device. sRAGE concentrations were assessed in frozen samples using enzyme-linked immunosorbent assay methods (R&D Systems). aPWV significantly (P<0.0001) increased across the sRAGE quartiles. An aPWV of 1 m s(-1) was associated with a 37% increase in the risk of low sRAGE (<918 pg ml(-1), bottom quartile; P-value=0.018). In a categorized manner, subjects in the bottom sRAGE quartile had an odds ratio of an increased aPWV (⩾9.3 m s(-1)), adjusted for all potential confounders of 2.05 (95% confidence interval: 1.26-3.32; P=0.004), but this was only the case for non-diabetic hypertensive patients. In contrast, a low sRAGE was rejected as an independent predictor of an increased aPWV in normotensive or diabetic subjects using similar regression models. In conclusion, low circulating sRAGE was independently associated with increased arterial stiffness in a general population-based sample, but this was only observed in hypertensive non-diabetic patients.


Application of conjoint liquid chromatography with monolithic disks for the simultaneous determination of immunoglobulin G and other proteins present in a cell culture medium.
The aim of this study was to develop a chromatographic method, as a substitute for enzyme-linked immunosorbent assays, for the rapid and simultaneous detection of IgG, insulin, and transferrin present in a cell culture medium. Conjoint liquid chromatography (conjoint LC) using monolithic disks was applied for this purpose. An anion-exchange disk was combined with a Protein G affinity disk in a preparative HPLC system. IgG bound to the Protein G disk, whereas transferrin and insulin were captured on the quaternary ammonium (QA) disk. Using this method, it was possible to simultaneously determine the concentrations of IgG, transferrin, and insulin in the cell culture medium. Thus, conjoint LC could be used for the rapid and simultaneous detection of different proteins present in a cell culture medium.


Virulence of variola viruses for suckling mice.
We report work done in 1971 to determine the quantitative virulence for suckling mice of 26 variola virus isolates from different countries and from cases of differing severity. Strains of recognized variola major and variola minor viruses differed up to 100-fold (expressed as the harmonic mean dose of inoculum which killed mice 2-4 d old, inoculated intracranially, in 5 d). Isolates from Indonesia and from East and West Africa gave intermediate values. Unlike tests on chick embryos, this test distinguished between African and Indonesian isolates.


Age effects on voxel-based relaxometry used for epileptic patients.
T2 voxel-based relaxometry (VBR) is a technique that allows for a quantitative, unbiased analysis of T2 relaxation time across the whole brain. Previous studies have shown that this technique is effective for clinical analysis of single patients; however, the effects of age normal age-related changes on these data were unknown. Our study was therefore designed to assess the effect of normal aging on VBR data. A linear regression with age as a predictor of T2 was run in both a (1) whole-brain voxel-based manner to determine regions which showed significant age-related change and subsequently (2) on a selection of regions-of-interest to allow for a more detailed analysis of the trends. T2 estimates showed a significant increase with age in the frontal lobe white matter and a significant decrease with age in the putamen with region-of-interest and voxel-based regressions (p<0.05). There was also a general trend for T2 to decrease in inferior temporal lobe grey matter in the voxel-based regression. Age causes changes in T2 relaxation time in healthy control subjects, with increases being observed in frontal lobe white matter and decreases in the putamen. These changes should be accounted for when interpreting single subject VBR data.


Enzymatic mechanisms regulating protein S-nitrosylation: implications in health and disease.
Nitric oxide participates in cellular signal transduction largely through S-nitrosylation of allosteric and active-site cysteine thiols within proteins, forming S-nitroso-proteins (SNO-proteins). S-nitrosylation of proteins has been demonstrated to affect a broad range of functional parameters including enzymatic activity, subcellular localization, protein-protein interactions, and protein stability. Analogous to other ubiquitous posttranslational modifications that are regulated enzymatically, including phosphorylation and ubiquitinylation, accumulating evidence suggests the existence of enzymatic mechanisms for regulating protein S-nitrosylation. In particular, studies have led to the identification of multiple enzymes (nitrosylases and denitrosylases) that participate in targeted S-nitrosylation or denitrosylation of proteins in physiological settings. Nitrosylases are best characterized in the context of transnitrosylation in which a SNO-protein transfers an NO group to an acceptor protein (Cys-to-Cys transfer), but examples of transnitrosylation catalyzed by metalloproteins (Metal-to-Cys transfer) also exist. By contrast, denitrosylases remove the NO group from SNO-proteins, ultimately using reducing equivalents derived from NADH or NADPH. Here, we focus on the recent discoveries of nitrosylases and denitrosylases and the notion that their aberrant activities may play roles in health and disease.


Antineutrophil cytoplasmic antibodies in children.
To define the diagnostic meaning of antineutrophil cytoplasmic antibodies (ANCA) positivity in children, we analysed 1485 consecutive sera sent for routine immunological investigation to our department from January to August 1996. Using this large screening, we identified the most typical clinical disorders associated with ANCA in childhood. Out of 1485 indirect immunofluorescence (IIF) tests for ANCA, 143 were ANCA positive, 70 had a cytoplasmic IIF pattern (c-ANCA), and 73 a perinuclear IIF pattern (p-ANCA). The ANCA associated diseases in childhood were cystic fibrosis (CF) (31 c-ANCA, 7 p-ANCA positive out of 71 CF children investigated), juvenile chronic arthritis (JCA) (21 p-ANCA positive out of 78), auto-immune hepatitis (AIH) (4 c-ANCA and 12 p-ANCA positive out of 19), and ulcerative colitis (UC) (2 c-ANCA, 5 p-ANCA positive out of 15). In cases of c-ANCA positivity we determined the antigenic specificity of ANCA for proteinase 3 and/or bactericidal/permeability increasing protein. Borderline anti-proteinase 3 levels were found in CF, and in high levels in one boy with Wegener granulomatosis. Bactericidal/permeability increasing protein was characteristic target antigen in children with CF. p-ANCA positive children were further tested for the specificity for myeloperoxidase, which was detected mostly in children with JCA. The spectrum of diseases associated with ANCA in children includes, besides the diagnostic associations typical for adults, several typical pediatric entities, mainly juvenile chronic arthritis and cystic fibrosis.


A new real-time PCR method for rapid and specific detection of ling (Molva molva).
Seafood fraud - often involving substitution of one species by another - has attracted much attention as it is prevalent worldwide. Whilst DNA analysis has helped to combat this type of fraud some of the methods currently in use are time-consuming and require sophisticated equipment or highly-trained personnel. This work describes the development of a new, real-time PCR TaqMan assay for the detection of ling (Molva molva) in seafood products. For this purpose, specific primers and a minor groove binding (MGB) TaqMan probe were designed to amplify the 81bp region on the cyt b gene. Efficiency, specificity and cross-reactivity assays showed statistically significant differences between the average Ct value obtained for Molva molva DNA (19.45±0.65) and the average Ct for non-target species DNA (38.3±2.8), even with closely related species such as Molva dypterygia (34.9±0.09). The proposed methodology has been validated with 31 commercial samples.


Deficient CCR7 signaling promotes TH2 polarization and B-cell activation in vivo.
The chemokine receptor CCR7 has a central role in regulating homing and positioning of T cells and DCs to lymph nodes (LNs) and participates in T-cell development and activation. In this study, we addressed the role of CCR7 signaling in T(H) 2 polarization and B-cell activation. We provide evidence that the lack of CCR7 drives the capacity of naïve CD4(+) T cells to polarize toward T(H) 2 cells. This propensity contributes to a lymph node environment in CCR7-deficent mice characterized by increased expression of IL-4 and increased frequency of T(H) 2 cells. We show that elevated IL-4 levels lead to B-cell activation characterized by up-regulated expression of MHC class II, CD23 and CD86. Activated B cells are in turn highly efficient in presenting antigen to CD4(+) T cells and thus potentially contribute to the T(H) 2 microenvironment. Taken together, our results support the idea of a CCR7-dependent patterning of T(H) 2 responses, with absent CCR7 signaling favoring T(H) 2 polarization, dislocation of T helper cells into the B-cell follicles and, as a consequence, B-cell activation.


Prion-like transmission of α-synuclein pathology in the context of an NFL null background.
Neurofilaments are a major component of the axonal cytoskeleton in neurons and have been implicated in a number of neurodegenerative diseases due to their presence within characteristic pathological inclusions. Their contributions to these diseases are not yet fully understood, but previous studies investigated the effects of ablating the obligate subunit of neurofilaments, low molecular mass neurofilament subunit (NFL), on disease phenotypes in transgenic mouse models of Alzheimer's disease and tauopathy. Here, we tested the effects of ablating NFL in α-synuclein M83 transgenic mice expressing the human pathogenic A53T mutation, by breeding them onto an NFL null background. The induction and spread of α-synuclein inclusion pathology was triggered by the injection of preformed α-synuclein fibrils into the gastrocnemius muscle or hippocampus in M83 versus M83/NFL null mice. We observed no difference in the post-injection time to motor-impairment and paralysis endpoint or amount and distribution of α-synuclein inclusion pathology in the muscle injected M83 and M83/NFL null mice. Hippocampal injected M83/NFL null mice displayed subtle region-specific differences in the amount of α-synuclein inclusions however, pathology was observed in the same regions as the M83 mice. Overall, we observed only minor differences in the induction and transmission of α-synuclein pathology in these induced models of synucleinopathy in the presence or absence of NFL. This suggests that NFL and neurofilaments do not play a major role in influencing the induction and transmission of α-synuclein aggregation.


Comparison of the Coagulation Profile of Adolescent Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion With and Without Tranexamic Acid.
Prospective, observational cohort study. To improve the understanding of coagulation and bleeding mechanisms during spinal deformity surgery. Fibrinolysis is the mechanism of bleeding for adolescent idiopathic scoliosis undergoing posterior spinal fusion. Antifibrinolytics have become popular; however, literature to support their use remains mixed. The mechanism of action has not been demonstrated. The coagulation profile of 88 adolescent idiopathic scoliosis patients undergoing posterior spinal fusion was analyzed. Standard coagulation laboratory investigations and thromboelastograms were drawn hourly through the case. Fifty-eight patients received no antifibrinolytic, whereas 30 patients received tranexamic acid by standardized protocol. The coagulation parameters, estimated blood loss, and transfusion requirements were compared in the two groups. The two cohorts had no differences in demographic or surgical characteristics. Mean age was 13.6 years, 83% were female, a mean of 11.1 levels were fused, and the mean duration of surgery was 209 minutes. The tranexamic acid cohort did not demonstrate a decrease in blood loss. The transfusion rate, however, dropped from 47% in the non-tranexamic acid cohort to 23% in the tranexamic acid cohort (p = .03). Standard coagulation parameters did not differ between the groups. Fibrinolysis was diminished in the tranexamic acid cohort as measured by a Fibrinolysis score (mean maximum value 2.0 without tranexamic acid vs. 0.7 with tranexamic acid, p < .0001) and the lysis percent at 30 minutes by thromboelastogram (elevated to 3.9% without tranexamic acid vs. 1.2% with tranexamic acid at the 3-hour mark, p = .05). This study provides confirmation of antifibrinolytic activity during posterior spinal fusion for adolescent idiopathic scoliosis. The presented data of fibrinolysis are proposed as standard measurements for future work on controlling blood loss during scoliosis surgery. Level 2, prospective comparative study.


A decision support tool has similar high PrEP uptake and increases early PrEP persistence in adolescent girls and young women in South Africa: results from a randomized controlled trial.
African adolescent girls and young women (AGYW) have high rates of HIV acquisition and are a priority population for HIV pre-exposure prophylaxis (PrEP). PrEP implementation has been limited by AGYW's low perceived HIV risk and provider demands. A decision support tool (DST) with information about PrEP could improve clients' risk perception, knowledge about PrEP, informed decision-making and motivation to use PrEP based on their risk, facilitating PrEP delivery in primary healthcare (PHC) clinics. We designed MyPrEP, a client-facing DST about PrEP and HIV prevention, with youth-friendly information and images. The impact of the MyPrEP tool was assessed among HIV-negative women aged 18-25 years presenting to a PHC clinic in Johannesburg, South Africa from March 2019 to 2020. AGYW were randomized by day to the DST or a general health website as the control condition. A clinician blinded to DST versus control allocation provided standard of care counselling about PrEP, offered PrEP, administered a questionnaire and conducted sexually transmitted infection testing. The primary outcome was PrEP initiation and the secondary outcome was PrEP persistence at 1 month, determined by pharmacy dispensation records. Of 386 AGYW screened, 353 were randomized (DST n = 172, control n = 181) with a median age of 21 years (interquartile range [IQR] 20, 23) and 56% (199/353) attending the clinic for HIV testing, 46% (164/353) using contraception, 15% (53/353) using condoms consistently and 37% (108/353) with a curable sexually transmitted infection. PrEP was initiated by 97% in the DST group and 94% in the control group (OR 1.79; 95% confidence interval, CI = 0.79-1.53), of whom two-thirds planned to continue PrEP until they decided if they liked PrEP. At 1 month, PrEP persistence was 19% in the DST and 10% in the control group (OR 1.97, 95% CI 1.08-3.69). Ninety-nine percent randomized to the DST reported satisfaction with MyPrEP. Among AGYW attending a South African PHC clinic, PrEP uptake was >90% with two-fold higher PrEP persistence at 1 month in those randomized to use the MyPrEP DST. Given the need for strategies to support PrEP implementation and improve low PrEP persistence among African AGYW, a PrEP DST warrants further evaluation.


Proportion and predictors of remission and recovery in first-episode psychosis: Systematic review and meta-analysis.
To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies. One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49-58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27-36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found. Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years.


Free os cuboideum secundarium: a case report.
The free os cuboideum secundarium is one of the most rare accessory bones of the foot and is located proximal and plantar to the cuboid. In a 9-year-old boy, a free os cuboideum secundarium of the left foot was resected for persistent pain after trauma. Histologic examination showed degenerative changes of the hyaline cartilage that covered the entire bone. The central spongiosa appeared normal. The patient is free of pain and is still playing football 9.5 years after resection of the accessory bone. Follow-up examination showed no clinical sign of pathology except a soft scar with little discomfort when walking without shoes. Radiographs showed complete remodeling of left cuboid and calcaneus with normal bony configuration of both feet.


Treatment for traumatic memories: review and recommendations.
The aim of this article is to provide recommendations concerning the use of exposure-based therapy for reduction of emotional responding to traumatic memories. Background for these recommendations consists of a summary of the literature on traumatic stress and symptoms of posttraumatic stress disorder (PTSD); an overview of biological, cognitive, and behavioral models for traumatic memory; and a selective review of evidence for the effectiveness of therapeutic exposure as a treatment for trauma memories and PTSD. The recommendations themselves demonstrate how clinical decision making during the course of treatment might be informed by empirical evidence and theoretical models concerning human memory, as well as ethical and legal considerations that mark this topic.


Q fever laboratory diagnostic methods used in Roumania.
The methods used presently in Roumania for Q fever laboratory diagnosis are presented. They include Coxiella (C.) burnetii isolation procedures, Q fever serologic tests, and the skin test. The diagnosis by isolation procedures is performed by inoculation into guinea pigs and embryonated eggs. Q fever serologic diagnostic tests are the complement fixation (CF), microagglutination (MA), and IgG-IgM ELISA tests. Results obtained by comparing the CF test with MA and ELISA tests in the diagnosis of acute cases and of previously infected patients are presented. Skin test diagnosis using a C. burnetii corpuscular antigen in animals and a soluble antigen in men was compared with the CF test and proved the reliability of the skin test as an alternative method for Q fever diagnosis, especially in epidemiologic investigations.