A Multicenter Collaborative Effort to Reduce Preventable Patient Harm Due to Retained Surgical Items.
Unintentional retention of surgical items is severe but preventable patient harm in surgical procedures. One multicenter health care organization experienced a harm event due to retained surgical items (RSIs) every eight days in 2019-2020. The research team sought to reduce the incidence of harm due to RSIs, improve near-miss reporting, and increase process reliability in operating rooms across the organization. A total of 114 health care facilities in the organization were invited to participate in a multistate, multicenter patient safety initiative to reduce patient harm caused by RSIs. A national-level workgroup comprising various disciplines proposed an evidence-based best practice bundle with five elements: surgical stop, surgical debrief, visual counter, imaging, and reporting of deviations. The workgroup ensured that extensive education and support were accessible to all the participating sites. The researchers monitored the process reliability of bundle elements and improvement milestones of all the sites, along with rates of harm related to RSIs. Implementing the evidence-based RSI reduction bundle across 114 health care facilities resulted in a 14.3% reduction in the rate of harm caused by RSIs and a 59.1% increase in RSI near-miss reporting. The compliance to the RSI bundle reached an average of 70.5%, and 63.2% of the facilities are actively performing Plan-Do-Check-Act (PDCA) cycles to improve bundle compliance continually. Implementation of an RSI bundle can be done reliably, can improve near-miss reporting, and can reduce patient harm. Variation in process reliability between centers suggests the significance of overcoming cultural and organizational barriers.


Fecal microbiota transplantation from young donor mice improves ovarian function in aged mice.
Advanced maternal age is characterized by declines in the quantity and quality of oocytes in the ovaries, and the aging process is accompanied by changes in gut microbiota composition. However, little is known about the relationship between gut microbiota and ovarian aging. By using fecal microbiota transplantation (FMT) to transplant material from young (5-week-old) into aged (42-week-old) mice, we find that the composition of gut microbiota in FMT-treated mice presents a "younger-like phenotype" and an increase of commensal bacteria, such as Bifidobacterium and Ruminococcaceae. Moreover, the FMT-treated mice show increased anti-inflammatory cytokine IL-4 and decreased pro-inflammatory cytokine IFN-γ. Fertility tests for assessing ovarian function reveal that the first litter size of female FMT-treated mice is significantly higher than that of the non-FMT group. Morphology analysis demonstrates a dramatic decrease in follicle atresia and apoptosis as well as an increase in cellular proliferation in the ovaries of the FMT-treated mice. Our results also show that FMT improves the immune microenvironment in aged ovaries, with decreased macrophages and macrophage-derived multinucleated giant cells (MNGCs). These results suggest that FMT from young donors could be a good choice for delaying ovarian aging.


[Examinations to cAMP-levels in plasma (author's transl)].
Plasma cAMP levels were measured by a competetive protein binding method in nine healthy volunteers every 30 minutes over a period of 24 hours under standardized conditions. No circadian variation was observed. Upright posture after 32 hours bedrest increased cAMP significantly.


Chorea-acanthocytosis presenting as motor neuron disease.
Chorea-acanthocytosis (ChAc) is a rare autosomal recessive disease characterized by involuntary movements, seizures, cognitive changes, myopathy, and axonal neuropathy. We report a patient who presented with gait impairment and dysarthria. Clinical and neurophysiological assessment disclosed upper and lower motor neuron signs suggestive of motor neuron disease (MND). Later observation of involuntary movements prompted further investigation. Acanthocytes were identified, and the patient's chorein level was low. Genetic studies identified a novel double heterozygous mutation of the chorein gene involving an exon-stop mutation associated with another mutation that can affect the normal splicing of the RNA. We speculate that this genetic mutation could cause the atypical presentation. ChAc should be included in the differential diagnosis of atypical MND.


Essential opaque bubble layer elimination with novel LASIK flap settings in the FS200 Femtosecond Laser.
The purpose of this study is to evaluate the extent and incidence of opaque bubble layer (OBL) using laser-assisted in situ keratomileusis (LASIK) flaps created with the Alcon/WaveLight® FS200 femtosecond laser as a result of a recent change in flap programming parameters aiming to reduce further the incidence and extent of OBL. Intraoperative digital images of flaps from 36 consecutive patients (72 eyes) subjected to bilateral femtosecond-assisted LASIK were analyzed using a proprietary computerized technique. The incidence and extent of OBL was measured and reported as a percentage of the entire flap area. Flap creation was performed with a 1.7 mm wide canal, implemented as an updated design intended to reduce the extent of OBL (group A). The same OBL parameters were investigated and compared in an age-matched and procedure-matched patients in whom the previous standard setting of a 1.3 mm wide canal was implemented (group B). In group A, the average extent of OBL was 3.69% of the flap area (range 0%-11.34%). In group B, the respective values were 6.06% (range 0%-20.24%). We found the difference to be statistically significant (one-tailed P = 0.00452). This study suggests that there is a significant reduction in the incidence and extent of OBL when novel LASIK flap ventilation canal parameters of width and spot line separation are used.


Fatal disseminated infection with human herpesvirus-6.
A 13-month-old immunocompetent girl had fever, rash, and multisystem disease, and she eventually died of cardiac failure. Autopsy revealed intracellular viral inclusions of the herpesvirus group, with results of in situ hybridization positive for human herpesvirus-6. This is apparently the first case of fatal disseminated herpesvirus-6 infection.


Central coherence in eating disorders: a systematic review.
This review systematically appraised the research evidence for local versus global information processing to test the hypothesis that people with eating disorders (ED) had weak central coherence. Searches on Medline, EMBASE, PsycINFO and ISI Web of Science databases were conducted in November 2006 and subsequently updated in September 2007. Each search was conducted in two steps: (1) neuropsychological tasks measuring central coherence and (2) words related to cognitive functioning in eating disorders. Data were summarized in a meta-analysis if the number of studies for a given test was >5. Data were extracted from 16 studies. Meta-analyses were conducted for four tasks obtaining moderate effect sizes. The majority of studies found global processing difficulties across the ED spectrum. The results are less clear regarding local processing. People with ED have difficulties in global processing. It is less certain as to whether they have superior local processing. Currently, there is insufficient evidence to refute the weak central coherence hypothesis.


Spinal anastomosed remnant imprints of vertebral veins linking the transverse foramina: a case report of a novel anatomic variant of the cervical venous plexus.
Despite various postulated classifications attempting to simplify the complex angioarchitecture of the cervical spine, the nomenclature of spinal variants and lesions remains inconsistent. Knowledge of variations in the anatomy of the vertebral veins will assist in avoiding complications during neck surgery and procedures such as vertebroplasty. In addition, venous variants may act as a route for the spread of infection, emboli, or metastases. Therefore, we report a novel variant encountered at our institution in this case report. We coincidentally discovered an original anatomical variant of the cervical venous plexus linking the transverse foramina in a Saudi man. We termed the variant "spinal anastomosed remnant imprints" (SARI), guided by the second edition of Terminologia Embryologica, a project of the Federative International Programme for Anatomical Terminology. This variant anastomoses with the vertebral veins at the same level, forming segmented osseous impressions. It shares a topographical relationship with the embryonic anterior cardinal veins, which normally regress in the prenatal period. We hypothesize that these intersegmental anastomosing veins do not always regress and may persist into adulthood, with individualized variations of the venous circulation. This report highlights an important finding of interpersonal anatomical variation of veins in the cervical spine, discovered with the aid of advanced imaging to distinguish it from pathological conditions. This will be of assistance to radiologists, anatomists, and clinicians in decision-making and to surgeons in planning for neck surgery.


Differential diagnosis and secondary causes of osteoporosis.
Secondary osteoporosis refers to osteoporosis in which an underlying cause or factor other than those attributable to the postmenopausal state or aging can be identified. Primary, or idiopathic, osteoporosis implies that a secondary cause cannot be found. Secondary osteoporosis occurs not only in postmenopausal women but also in men and premenopausal women. In series reported from specialized centers, as many as 30% of postmenopausal women and 50% to 80% of men have an identifiable secondary cause of osteoporosis, although the frequency of secondary osteoporosis is probably much lower in the general population. In assessing the patient with osteoporosis, it is important to look for secondary causes and aggravating factors that are reversible and amenable to therapy. In addition to secondary forms, 2 metabolic bone diseases, osteomalacia and primary hyperparathyroidism, can mimic or aggravate osteoporosis. This paper will summarize the differential diagnosis and management of osteoporosis, osteomalacia, and hyperparathyroidism and review the most common causes of secondary osteoporosis.


Modulation of 3H-prostaglandin E2 binding sites in the rabbit gastric mucosa.
The binding of 3H-prostaglandin E2 (PGE2) to rabbit gastric mucosa was investigated. Binding depended on incubation time, temperature and pH, and was saturable and reversible. Scatchard plot analysis revealed a single class of binding sites with a dissociation constant (Kd) of 5.33 +/- 0.21 nM and a maximum number of binding sites (Bmax) of 138.1 +/- 3.4 fmol/mg protein. PGE1 and 16,16-dimethyl PGE2 potently competed with 3H-PGE2 for the binding sites of gastric mucosa, whereas PGA2, PGF2 alpha, 6-keto PGF1 alpha and thromboxane B2 were less potent. The gastric mucosa prepared from the rabbits given indomethacin (5 mg/kg s.c. three times) showed a lower Kd (2.47 +/- 0.19 nM) for 3H-PGE2 than that from untreated one. Treatment with a PGE1 analog, misoprostol (320 micrograms/kg s.c. three times) lowered the Bmax to 74.1 +/- 2.4 fmol/mg protein without any significant effect on the Kd value. It is concluded that rabbit gastric mucosa has specific binding sites for 3H-PGE2 which may be modulated by the levels of PGs in vivo.


Three-dimensional simulation of reservoir temperature and pollutant transport by the lattice Boltzmann method.
Predicting the three-dimensional (3D) transport processes of reservoir temperature and pollutants is essential for water environmental protection and restoration, and introducing the lattice Boltzmann (LB) method into this prediction is necessary because of its simple algorithm, straightforward implementation of boundary conditions, and high computation efficiency. In this paper, a triple-distribution function (TDF) LB model for flow-temperature-concentration coupling simulations is introduced. Some essential techniques for implementing this method in 3D reservoirs are also described, including the treatment of water surface fluctuation, the consideration of surface heat exchange, and the hardware acceleration using the graphics processing unit (GPU). Two cases verified the proposed model, and then, the temporal-spatial variations of flow, temperature, and pollutants in the upper reservoir of a pumped-storage power station during both pumping and generating modes were analyzed to demonstrate its applicability. In the reservoir, the water forms several circulations, the cold water from the inlet flows as an undercurrent firstly, and then spread laterally, and the spreading of pollutants directly relates to the flow velocity. The results of flow, temperature, and concentration fields in different working conditions are consistent with model tests and physical laws, which shows good prospects of the proposed LB model.


Increase in body weight of spontaneously hypertensive rats (SHR) under prolonged behavioral stimulation.
We noticed that during 44 weeks of exposure to a number of behavioral tests (such as assessments of emotionality, locomotion, short term memory and visual discrimination learning) the body weight of spontaneously hypertensive rats (SHR) increased above that of normotensive controls (NT). To determine whether this difference was related to "behavioral stimulation" resulting from different testing situations and accompanying handling, body weights were recorded in other SHR and NT groups not subjected to any experiment (unstimulated). Stimulated SHR were significantly heavier than rats from other subgroups (unstimulated SHR as well as stimulated and unstimulated NT rats) which did not differ from one another. The first significant difference appeared after 7 weeks of behavioral training (18th week of life). Several weeks later, and continuing for the duration of study, stimulated SHR were approximately 12% heavier than the other 3 groups. No effect of behavioral testing on blood pressure was seen in either strain.


A Comparison of Geriatric Hip Fracture Databases.
The National Surgical Quality Improvement Project (NSQIP) and the Trauma Quality Improvement Project (TQIP) collect data on geriatric hip fractures (GHFs) that could be used to generate risk-adjusted metrics for care of these patients. We examined differences between GHFs reported by our own trauma center to the NSQIP and TQIP and those vetted through an internal GHF list. We reviewed charts of GHFs treated between January 1 and December 31, 2015, and compared patients in an internal GHF database and/or reported to the NSQIP and/or TQIP and determined differences between databases. We identified 89 "true" GHFs, of which 96% were identified by our institutional database, 70% by NSQIP, and 9% by the TQIP. No differences were found in outcomes and total costs. The net revenue/patient in the NSQIP database was $24,373 more than those in the institutional database. Caution should be taken when using NSQIP/TQIP databases to evaluate the care of GHFs. Level III.


Normalizing for biology: accounting for technical and biological variation in levels of reference gene and insulin-like growth factor 1 (igf1) transcripts in fish livers.
Feeding, fasting and re-feeding is a common experimental paradigm for studying growth endocrinology. Herein we demonstrate dynamic changes in the livers of coho salmon under these conditions and how changes in liver composition can influence quantification and interpretation of liver gene expression data. A three-week fast resulted in decreases in hepatosomatic index (liver size), liver glycogen content, and liver DNA concentration. In addition, significant differences were found in liver transcript levels from fed and fasted fish for the reference genes, arp and ef1a, when these were normalized to total RNA. We took the additional step of normalizing reference gene transcript levels to the liver homogenate RNA/DNA ratio to account for differences in RNA yield/cell and the number of cells sampled, normalizing to transcript number per cell rather than transcript number per unit RNA. After this additional step no significant differences in liver transcript levels of reference genes were found. The significance of these results was illustrated by normalizing liver transcript levels of insulin-like growth factor 1 (igf1) to ef1a transcript levels or ef1a transcript levels by RNA/DNA. The different normalization strategies resulted in differing patterns of change in igf1 transcript levels between fed and fasted fish. The novelty of this work rests in a two-step normalization process, attempting to account for both 1) technical errors in reverse transcription and qPCR reactions, and 2) biological variance in liver samples.


The ototoxic effect of cisplatin on guinea pigs in relation to dosage.
The effect on the electrophysiological hearing thresholds and the endocochlear DC potential (EP) was studied in four groups of guinea pigs receiving different doses of cisplatin. By multiple low-dose intraperitoneal injections a permanent hearing loss was produced without a permanent decrease of the EP. On the other hand, when cisplatin was given as a single high-dose intravenous injection, there was an impairment of the electrophysiological hearing thresholds and EP, depending upon the level of cisplatin dose. It is concluded that cisplatin-induced hearing loss is not necessarily a sequela to a loss of EP.


Disparities in surgical outcomes for low socioeconomic status patients in Australia.
There are disparities in surgical outcomes for patients of low socioeconomic status globally, including in countries with universal healthcare systems. There is limited data on the impact of low socioeconomic status on surgical outcomes in Australia. This study examines surgical outcomes by both self-reported unemployment and neighbourhood level socioeconomic status in Australia. A retrospective administrative data review was conducted at a tertiary care centre over a 10-year period (2008-2018) including all adult surgical patients. Multivariable logistic regression adjusting for year, age, sex and Charlson Comorbidity Index was performed. 106 197 patients underwent a surgical procedure in the decade examined. The overall adverse event rates were mortality (1.13%), total postoperative complications (10.9%), failure to rescue (0.75%) and return to theatre (4.31%). Following multivariable testing, unemployed and low socioeconomic patients had a higher risk of postoperative mortality (OR 2.06 (1.50-2.82), OR 1.37 (1.15-1.64)), all complications (OR 1.43 (1.31-1.56), OR 1.21 (1.14-1.28)), failure to rescue (OR 2.03 (1.39-2.95), OR 1.38 (1.11-1.72)) and return to theatre (OR 1.42 (1.27-1.59), OR 1.24 (1.14-1.36)) (P < 0.005 for all). Despite universal healthcare, there are disparities in surgical adverse events for patients of low socioeconomic status in Australia. Disparities in surgical outcomes can stem from three facets: a patient's access to healthcare (the severity of disease at the time of presentation), variation in perioperative care delivery, and social determinants of health. Further work is required to pinpoint why these disparities are present and to evaluate the impact of strategies that aim to reduce disparities.


Imaging dynamic cell signaling in vivo with new classes of fluorescent reporters.
Dynamical features of cell signaling are the essence of living organisms. To understand animal development, it is fundamental to investigate signaling dynamics in vivo. Robust reporters are required to visualize spatial and temporal dynamics of enzyme activities and protein-protein interactions involved in signaling pathways. In this review, we summarize recent development in the design of new classes of fluorescent reporters for imaging dynamic activities of proteases, kinases, and protein-protein interactions. These reporters operate on new physical and/or chemical principles; achieve large dynamic range, high brightness, and fast kinetics; and reveal spatiotemporal dynamics of signaling that is correlated with developmental events such as embryonic morphogenesis in live animals including Drosophila and zebrafish. Therefore, many of these reporters are great tools for biological discovery and mechanistic understanding of animal development and disease progression.


Screening for HIV protease inhibitors by protection against activity-mediated cytotoxicity in Escherichia coli.
Expressed retroviral proteases are often cytotoxic to the hosts. The cytotoxicity of a tethered dimer HIV protease described previously is particularly severe that transformed Escherichia coli cells could not survive the bactericidal activity of the low-level protease produced under uninduced conditions. The presence of HIV protease inhibitors protected the transformed cells from cytotoxic effects and allowed the growth of these cells on plates and in broth. A high throughput screening method was developed to seek compounds that served as "growth factors" for the HIV protease restricted cells. Several compounds identified by this screening supported the growth of these cells, preserved their viability, and inhibited HIV protease. This assay could be used as a general method for screening for inhibitors of recombinant enzymes that produce a cytotoxic phenotype in host cells.


Determinants and functional impact of restrictive physiology after repair of tetralogy of Fallot: new insights from magnetic resonance imaging.
The presence of end-diastolic forward flow (EDFF) in the pulmonary arteries is commonly regarded as a hallmark of restrictive physiology of the right ventricle (RV) which, in turn, has been associated with a better long-term prognosis in patients after TOF repair. However, controversy persists over the beneficial clinical consequences of restrictive physiology. We aimed at determining the clinical relevance of restrictive physiology late after TOF repair. Fifty magnetic resonance examinations of 50 patients (age 13.0 ± 2.8 years, 26 males) with repaired TOF were evaluated. The patients were divided into: Group-1 with and Group-2 without EDFF; Group-A with smaller RVs (<170 ml/m2) and Group-B with larger RVs (≥ 170 ml/m2). Maximum oxygen consumption as percent of predicted (VO2max-pred) at a recent exercise test was recorded. Groups-1 and 2 did not differ with regard to their right ventricular end-diastolic volume, pulmonary regurgitant volume, or QRS duration. Patients in Group-1 had a higher VO2max-pred than patients in Group-2 (70.3% versus 54.7% of predicted, p<0.01). In Group-1A versus 2A (RV<170 ml/m(2), with and without EDFF) this difference persisted, but in Group B there was no difference in VO2max-pred between patients with and without EDFF. The flow volume of EDFF correlated with VO2max-pred (r=0.444, p=0.007). End-diastolic forward flow measured by magnetic resonance is present in patients with small and large RVs. The presence of EDFF is associated with better exercise tolerance, but only in patients with relatively small RVs.


MicroRNA-24-3p alleviates hepatic ischemia and reperfusion injury in mice through the repression of STING signaling.
Ischemia and reperfusion (I/R) injury is a common cause of hepatocyte injury and liver dysfunction during liver transplantation, but its mechanism is needed further explored. We aimed to investigate whether STING pathway activation is involved in the liver I/R and further determine the role of the microRNA(miR)-24-3p in liver I/R injury in mice. Our data showed that STING mRNA level was negatively related with miR-24-3p in livers of I/R-treated mice. Next, we identified that STING could be bound by miR-24-3p by bioinformatic and luciferase report assay. Moreover, downregulation of STING alleviated the protein expression of p-IRF3 and the serum level of inflammatory factor and aminotransferase in I/R mice model. Furthermore, transfection of I/R treated mice with exogenous miR-24-3p significantly inhibited the protein expression of STING and p-IRF3 in liver, and attenuated serum inflammatory cytokines release, as well as the dysfunction and apoptosis of liver in I/R model in vivo. This study suggests that miR-24-3p may ameliorate inflammatory response and cellular apoptosis in hepatic I/R process by targeting STING, which might be a potential therapeutic target for preventing liver I/R development and progression.


Photothermal-based nanomaterials and photothermal-sensing: An overview.
Based on the excellent properties, photothermal nanomaterials have been widely used in many fields, such as trace substance detection, optical imaging, medical diagnosis and treatment. Different from colorimetric, fluorescent and electrochemical methods which often suffer from the problems of high background interference, operation procedure dependence and high cost, photothermal sensing can effectively break the limitations of the above methods and become an alternative strategy due to its high resolution and spatial controllability. Especially in recent years, the continuous development of new materials and the introduction of portable, low-cost and precision photothermal measuring equipment can significantly improve the application potential of photothermal detection. Here, we conducted comprehensive analyses on those studies. This review summarized the progress of photothermal detection over recent years, including the main types of photothermal nanomaterials and the generation principle of the photothermal effect, the relevant matching thermometry tools, and the applications in the designing of sensing strategies. It aims to provide a reference for researchers to synthesize nanomaterials with stable and high photothermal conversion efficiency and develop more effective and sensitive detection methods.


Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombotic events.
To determine the relationship between the presence of antiphospholipid (aPL) antibodies, hydroxychloroquine use and the occurrence of thrombotic events in patients with systemic lupus erythematosus (SLE). Four hundred and forty-two SLE patients from the LUMINA (Lupus in Minorities: Nature vs Nurture) cohort, a multiethnic (Hispanics from Texas, n = 99 and Puerto Rico, n = 36; African Americans, n = 172; and Caucasians, n = 135) cohort, were studied by generalized estimating equation (GEE) to determine the relationship between antiphospholipid (aPL) antibodies (measured as IgG and IgM aPL antibodies and/or the lupus anticoagulant) at enrolment or historically prior to enrolment, hydroxychloroquine use (ever) and the occurrence of thrombotic (central and/or peripheral, arterial and/or venous) events after adjusting for known and possible confounders [socioeconomic-demographic features, smoking, disease activity and damage, serum cholesterol levels, anti-oxidized low-density lipoprotein IgG and IgM antibodies, and high-sensitivity (hs) C-reactive protein]. Postanalysis correlation between aPL and anticardiolipin (aCL) assays was attempted by performing aCL assays on random samples of patients whose aPL status was known. A number of clinical variables were significant in the univariable analyses; however, in the multivariable GEE analyses, only smoking [odds ratio (OR) 2.777, 95% confidence interval (CI) 1.317-5.852] and disease activity as measured by the SLAM (Systemic Lupus Activity Measure) (OR 1.099; 95% CI 1.053-1.147) were significant. In particular, hydroxychloroquine use, which appeared to be protective against thrombotic events in the univariable analyses, was not retained in the multivariable analyses. aPL antibodies were not significant in either analysis. Few additional aPL-positive patients emerged from the validation study. Smoking and disease activity emerged as important determinants in the occurrence of thrombotic events in our patients. Comprehensive treatment strategies should be directed to both smoking cessation and control of disease activity in patients with SLE.


Construction and identification of the recombinant hFcεRIα/RBL-2H3 cells.
IgE/FcεRI signal pathway plays a crucial role in triggering allergic reactions, and there is no cross-recognition between IgE and FcεRI in human and rats. In order to obtain the hFcεRIα/ RBL-2H3 cell line, total RNA was extracted from U937 cells, and the human FcεRIα gene was obtained by RT-PCR technology. Then the amplified product was digested and inserted into the pIRES2-EGFP vector. After the plasmid was transfected into the RBL-2H3 cells using lipofectamine, and the RBL-2H3 cell lines of stable expression were screened by G418. The transfection efficiency reached 60.45% with optimizing transfection parameters. The last the expression of hFcεRIα was detected by RT-PCR, western blotting and fluorescent microscopy. The present results demonstrated that the pIRES2-EGFP-hFcεRIα vector was constructed and a stable cell line of hFcεRIα/ RBL-2H3 cells was established successfully. This cell line is promising tools for further research on the pathogenesis and drug development of allergic diseases.


WITHDRAWN: Identification of microRNA precursor based on gapped n-tuple structure status composition kernel.
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Polymicrobial seminal vesical abscess in a kidney transplant recipient.
Seminal vesicle abscess is extremely rare and is associated with specific predisposing conditions. Here we report a polymicrobial seminal vesicle abscess in a kidney transplant recipient that was not associated with any of the known precipitating events.


Standardization of 65Zn.
Two absolute methods were used for standardizing the 65Zn solution received within the framework of the 2002-2003 full-scale BIPM comparison. The first method was the 4piPC-gamma-coincidence with efficiency extrapolation. The measurement conditions were adjusted so that the slope of the extrapolation curve was absent, which ensured that the measurement result did not depend on the positron branch intensity. When using the second method, the KX-gamma-coincidence counting with two NaI(Tl) scintillation crystals of different thicknesses, extrapolation was not needed, but a correction for the positron branch was necessary. It is shown that the 4piPC-gamma-coincidence method has a significantly larger uncertainty, and it is necessary to pay attention to the uncertainty component connected with setting the gamma-channel mode, which is characteristic for 65Zn only.


Comparison of effects of ingested medium- and long-chain triglyceride on gallbladder volume and release of cholecystokinin and other gut peptides.
In a double-blind, crossover study of the effect of ingested medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) in six normal subjects, the gallbladder did not contract after ingestion of MCT but instead had significantly increased in volume at 2 hr after the meal. Plasma cholecystokinin (CCK) increased after the MCT meal, but gastrin, motilin, pancreatic polypeptide (PP), and GIP were unaffected. The long-chain triglyceride meal evoked a brisk and sustained gallbladder contraction, higher levels of CCK, and a significant increase in plasma PP and GIP levels.


Ecological niche modeling of the pantropical orchid Polystachya concreta (Orchidaceae) and its response to climate change.
Climate is the dominant control factor on the spatial distribution of organisms on a global scale and global warming is predicted to become a major cause of species extinctions. In our study ecological niche modeling (ENM) was used to estimate the effect of projected future climate changes on the pantropical orchid Polystacha concreta as well as to reconstruct changes in the distribution of the suitable climatic niches of this species since the Last Glacial Maximum (LGM). The study revealed small differences in the niches occupied by populations of P. concreta recorded in various continents; however, these alterations will become more significant in regard to future climatic change. While losses of suitable habitats of the studied orchid will occur in the Americas and Africa, global warming will be favorable for Asian populations. Our study suggests a significant loss of niches since the LGM which indicates that the currently observed loss of habitats is not only the result of human activity but also of natural changes of the Earth's climate. From the obtained models we identified the areas that will be the most resistant regarding the modifications caused by climate change.


Improving visualization of trace components for quantification using a power law based integration approach.
In some cases, trace component analysis only requires a sensitive and high-resolution mass spectrometer. However, enantiomers must be completely separated to be differentiated with a mass spectrometer, which is highly dependent on the stationary-mobile phase composition. In case of a challenging chiral separation, instead of trying new columns for screening purpose, resolution enhancement techniques could be used to resolve partially overlapping peaks. A well-known enhancement method is the power law, which increases the linear dynamic range of each analyte and reduces excessive noise. In many cases, the peak noise can decrease significantly by applying the power law. However, the main drawback is that this approach changes relative peak areas and heights of each peak in a non-linear fashion which limits its use for quantitative purposes. In this study, a normalized power law was utilized for extracting correct area information. It is a simple (5 step) protocol that only requires Microsoft Excel, and results in enhanced visualization of trace components, especially in low signal/noise environments, and makes integration convenient and reproducible. Several difficult chiral trace component analyses were investigated, including applications pertaining to ultrafast high-throughput chromatography, enantiopurity, and peak purity analysis. For complicated cases with multiple overlapped peaks of different resolutions, a segmented normalized power law was utilized. A trace component coeluting near a dead volume peak and a trace enantiomeric component in the tail of the corresponding enantiomeric peak were virtually enhanced. As an additional tool, first and second derivatives were utilized to identify if an enantiomeric impurity is coeluting with the dominant enantiomer under overload conditions. Idiosyncrasies of the derivative test are discussed. This study shows how these simple approaches can be used for accurate quantitation, specifically for trace enantiomeric components.


Kinetic analysis of impaired work-cost performance in jaundiced rabbit liver.
Impairment of energy metabolism was studied in jaundiced rabbit liver by kinetic analysis of energy transfer function. Free cytosolic ADP (ADPf), as calculated from the measured components of the glyceraldehyde-3-phosphate dehydrogenase and 3-phosphoglycerate kinase/lactate dehydrogenase reactions, decreased from the control value of 48.1 to 37.0 microM at 24 h after bile duct ligation. The maximal velocity (Vmax) of ATP synthesis, as measured by state 3 respiration of isolated mitochondria, decreased from the control value of 62.1 to 38.3 nmol ATP synthesized per min per mg mitochondrial protein, while the Michaelis constant for ADP (Km) decreased from the control value of 19.2 to 12.8 microM. ATP synthesis velocity in vivo }v: Vmax/[1 + (Km/[ADPf])], as calculated by Vmax, Km and ADPf, decreased from the control value of 44.4 to 28.5 nmol ATP synthesized per min per mg mitochondrial protein. Delta v/delta ADPf(delta v/delta ADPf: Vmax.Km/(Km + [ADPf])2), which indicates work-cost performance of the liver, decreased from the control value of 0.263 to 0.198. Biochemical output of the liver, as measured by hippurate synthesis from benzoate, decreased from the control value of 98.4 to 32.7 mg/h. These results indicate that synergistic decreases in ADPf, Vmax, v and delta v/delta ADPf take place in the course of deterioration of mitochondrial ATP synthesis and work output in jaundiced liver.


Prevalence and Genotyping of Anaplasma phagocytophilum Strains from Wild Animals, European Bison (Bison bonasus) and Eurasian Moose (Alces alces) in Poland.
Wild large ungulates, like European bison (Bison bonasus) and Eurasian moose (Alces alces), form an important part of the circulation of Anaplasma phagocytophilum, a Gram-negative, intracellular, tick-transmitted bacterium, in the natural environment. Bison and moose tissue samples were subjected to 16S rDNA, groEL and ankA partial gene marker amplification with specific primers using various variants of PCR. Out of 42 examined individuals, Anaplasma sp. were detected in 4/13 Eurasian moose (31%) and 7/29 European bison (24%). In addition, 12 groEL and 5 ankA partial gene positive samples were obtained from the examined animals. The phylogenetic analysis of the groEL partial gene classified samples from European bison to ecotype I, and samples from Eurasian moose to ecotype I and II; the analysis of the ankA partial gene assigned the samples to clusters I and IV. This study extends knowledge about A. phagocytophilum in wild large ungulates in Poland. This is the first report about the occurrence of Anaplasma sp. in one of the largest populations of free living European bison in the world. Our findings confirm that strains of A. phagocytophilum from Bison bonasus and Alces alces may constitute a natural reservoir of pathogenic HGA Anaplasma strains.


A snapshot of Australian primary health care nursing workforce characteristics and reasons they work in these settings: A longitudinal retrospective study.
This article aimed to provide a snapshot of demographics and professional characteristics of nursing and midwifery workforce in Australian primary health care (PHC) settings during 2015-2019 and factors that influenced their decisions to work in PHC. Longitudinal retrospective survey. Longitudinal data that were collected from a descriptive workforce survey were retrieved retrospectively. After collation and cleaning, data from 7066 participants were analysed using descriptive and inferential statistics in SPSS version 27.0. The majority of the participants were female, aged between 45 and 64 years old and working in general practice. There was a small yet steady increase in the number of participants in the 25-34 age group and a downward trend in the percentage of postgraduate study completion among participants. While factors perceived most/least important to their decision to work in PHC were consistent during 2015-2019, these factors differed among different age groups and postgraduate qualification holders. This study's findings are both novel and supported by previous research. It is necessary to tailor recruitment and retention strategies to nurses/midwives' age groups and qualifications to attract and retain highly skilled and qualified nursing and midwifery workforce in PHC settings.


Variables altering the impact of respiratory gated CT simulation on planning target volume in radiotherapy for lung cancer.
Respiratory gated CT simulation (4D-simulation) has been evolved to estimate the internal body motion. This study aimed to evaluate the impact of tumor volume and location on the planning target volume (PTV) for primary lung tumor when 4D simulation is used. Patients who underwent CT simulation for primary lung cancer radiotherapy between 2012 and 2016 using a 3D- (free breathing) and 4D- (respiratory gated) technique were reviewed. For each patient, gross tumor volume (GTV) was contoured in a free breathing scan (3D-GTV), and 4D-simulation scans (4D-GTV). Margins were added to account for the clinical target volume (CTV) and internal target motion (ITV) in 3D and 4D simulation scans. Additional margins were added to account for planned target volume (PTV). Univariate and multivariate analyses were performed to test the impact of the volume of the GTV and location of the tumor (relative to the bronchial tree and lung lobes) on PTV changes by more than 10% between the 3D and 4D scans. A total of 10 patients were identified. 3D-PTV was significantly larger than the 4D-PTV; median volumes were 182.79 vs. 158.21 cc, p = 0.0068). On multivariate analysis, neither the volume of the GTV (p = 0.5027) nor the location of the tumor (peripheral, p = 0.5027 or lower location, p = 0.5802) had an impact on PTV differences between 3D-simulation and 4D-simluation. The use of 4D-simulation reduces the PTV for the primary tumor in lung cancer cases. Further studies with larger samples are required to confirm the benefit of 4D-simulation in decreasing PTV in lung cancer.


Overall study of the in vitro plasma clotting system in an invertebrate, Liocarcinus puber (Crustacea Decapoda): considerations on the structure of the Crustacea plasma fibrinogen in relation to evolution.
An overall study of the in vitro plasma coagulation system in the crab Liocarcinus puber has been carried out using various analytical methods, namely thromboelastography, spectrophotometrical examination, and a new one based on changes of the mechanical impedance of the developing clot. From the results reported here the clotting pattern in this species appears surprisingly complex for an invertebrate and unexpectedly closer to that of the vertebrates. Indirect evidences suggest that the fibrinogen polypeptide chains in this species and very likely in the other crustacean, are very different from those of the vertebrates. This would imply that crustacean and vertebrate fibrinogen would have diverged from one another in a far remote past, far beyond the individualization of the vertebrate alpha chain, that is, over 1.5 million years ago.


Short latency somatosensory evoked potentials to median nerve stimulation: effect of low frequency filter.
The effect of low frequency filter bandpass restriction on median nerve short latency somatosensory evoked potentials was studied in 19 normal adult subjects. Components recorded with open bandpass (5-3000 Hz) were designated by numerical subscript (e.g. N20) and components recorded with restricted bandpass (150 or 300-3000 Hz) were designated by numerical superscript (e.g. N20). In open bandpass recordings, the response consisted of 3 positive potentials, the third of which was sometimes bilobed (P9, P11, P13, P14), followed by negative, positive, and negative potentials (N20, P23, N30). In restricted bandpass recordings the first three positive potentials were well defined and the N20 component was fractionated into 3 components (n16, N18, N20). N20 was followed by P21 and N23. Scalp distribution studies showed that N16 was widely distributed over the scalp but was slightly more prominent over primary somesthetic scalp regions contralateral to the side of stimulation which is consistent with an origin in caudal thalamocortical radiations. N18 and N20 were localized to somesthetic scalp regions contralateral to the side of stimulation suggesting an origin in terminal thalamocortical radiations or cerebral cortex. Open pass P23 and N30 and restricted pass P21 and N23 recorded over somesthetic scalp regions contralateral to the side of stimulation were often associated with components of similar latency but opposite polarity recorded over frontal scalp regions. Low amplitude fast frequency components were sometimes recorded between 25 and 40 msec in restricted bandpass recordings. These findings show that N20 arises in multiple generator sources of both far- and near-field origin and that multiple generators contribute to the SEP within 10-15 msec of the arrival of the volley in cerebral cortical elements. Since bandpass restriction selectively affects slow frequency activity which reflects primarily synaptic events rather than fast frequency activity which reflects axonal events, the use of bandpass restriction may aid in differentiating between these different types of activity.


Intrasession reliability of force platform parameters in community-dwelling older adults.
To investigate the intrasession reliability of center of pressure (COP) parameters calculated from force platform measurements. A cross-sectional study. Gait and balance laboratory. Community-dwelling healthy older adults (N=63) above the age of 62 years (mean age, 78.74 y). Not applicable. COP was estimated from a force platform, and the following parameters were calculated: (1) the total length of the COP displacement, (2) area of sway, (3) length of the COP displacement in the sagittal plane, and (4) length of the COP displacement in the frontal plane. Intraclass correlation coefficients (ICCs) were calculated by using 3 successive trials with 4 different test conditions. The test conditions were (1) normative standing with eyes open, (2) normative standing with eyes closed, (3) narrow stance with eyes open, and (4) narrow stance with eyes closed. The ICCs for the tests with eyes closed (.710-.946) were higher than those for tests with eyes open (.841-.945). The highest value was obtained for the vector sum of the COP during anteroposterior movement in narrow stance with eyes closed (.946). The value .710 was the lowest of all parameters and was an outlier for the narrow stance with eyes closed test, which was otherwise very reliable. Eight of 16 calculated ICCs showed excellent reliability (>.90). They can be recommended for further use in clinical trials. Tests with closed eyes were more reliable than tests with eyes open. We recommend using eyes closed test conditions when assessing static balance control. For these tests, all the calculated ICCs were over .90, except for measurements of sway area.


Association of VA Surgeons annual resident paper award winners: career paths following completion of postgraduate training.
The aims of this study are to track those AVAS podium resident prize winners and to determine patterns of fellowship training type of practice, and primary area of specialization and whether their prize winning paper reflects their current area of specialization today. We also determined whether these residents, once completing their training, ever practiced at a VA hospital, and, whether they have been or currently are members of the AVAS. There have been 43 residents who have won 46 podium awards during this 18 year period. Three/46 (6%) awards were won by a resident twice during different years. Among the 42 locatable residents, 3/42 (7%) are still in surgery training. Among those 39 who are in practice, 30/39 (76%) undertook a clinical fellowship and 22/39 (56%) are in an academic setting. Only 3/39 (8%) has ever worked at a VA hospital; all 3 are currently members of the AVAS. Among those with a specific area of clinical or research specialization (n = 32), in 25/32 (78%), their paper reflects their current area of specialization. Among our cohort of annual AVAS resident prize winners most have taken fellowship training. Greater than 50% pursue academic practice. Among those with an area of specialization, their prize winning paper reflects on their current area of specialization today. Few have ever worked in a VA hospital and thus few have ever been members of the AVAS.


Results of 226 patients with T3 laryngeal carcinoma after treatment with transoral laser microsurgery.
The purpose of this study was to assess the feasibility of transoral laser microsurgery (TLM) in treatment of pT3 laryngeal cancer. We conducted a retrospective case series study of 226 patients with pT3 glottic (n = 122; 54%) or supraglottic laryngeal carcinoma (n = 104; 46%). All patients were treated by TLM in combination with neck dissection (63%) and with postoperative radiotherapy (18%). Our main outcome measures were local control, organ preservation, functional outcome, overall survival, recurrence-free survival, and disease-specific survival. Median follow-up period was 57.8 months. The 5-year organ-preservation and local control rates for all patients were 87% and 71.4%, respectively. The 5-year overall, recurrence-free, and disease-specific survival were 64.4%, 63.0%, and 83.3%, respectively. Results are comparable to partial or total laryngectomy, while being superior to primary chemo(radio)therapy. TLM results in low morbidity, rapid recovery, and good function and can be a valid option for organ-preserving surgery of pT3 glottic and supraglottic cancer.


IBI379, a novel B cell maturation antigen/CD3 bispecific T-cell engager, displays high antitumor efficacy in preclinical models of multiple myeloma.
Multiple myeloma (MM) is a hematological malignancy that results from the malignant proliferation of plasma cells in the bone marrow. B cell maturation antigen (BCMA) is highly selectively expressed in malignant plasma cells and is a novel therapeutic target for MM. Here, we developed a bispecific T cell engager, IBI379, that targets BCMA and CD3, and investigated its antitumor efficacy against MM. IBI379 showed strong binding affinity with both BCMA and CD3, which triggered T cell activation, proliferation, and cytokine release. An in vitro study demonstrated that IBI379 induced the lysis of MM cells expressing differing levels of BCMA on the cell surface. Administration of IBI379 in H929 or Daudi-BCMA cell xenograft mouse models significantly inhibited tumor growth without inducing body weight loss. The mechanism of action study revealed the accumulation of CD4+CD8+ T cells and granzyme B-positive T cells in tumors that were treated with IBI379. Moreover, administration of low dose of IBI379 in cynomolgus monkeys was well-tolerated and induced the depletion of BCMA+ B cells and a mild transient increase of cytokines. Collectively, these results demonstrate that IBI379 is a highly potent therapeutic strategy for depleting BCMA-positive B cells and is a promising approach for the treatment of MM.


Estimation of hospital visits for respiratory diseases attributable to PM10 from vegetation fire smoke and health impacts of regulatory intervention in Upper Northern Thailand.
The air quality in Upper Northern Thailand (UNT) deteriorates during seasonal vegetation fire events, causing adverse effects especially on respiratory health outcomes. This study aimed to quantitatively estimate respiratory morbidity from vegetation fire smoke exposure, and to assess the impact of a burning ban enforced in 2016 on morbidity burden in UNT. We computed daily population exposure to fire-originated PM10 and estimated its health burden during a 5-year period from 2014 to 2018 using daily fire-originated PM10 concentration and the concentration-response function for short-term exposure to PM10 from vegetation fire smoke and respiratory morbidity. In subgroups classified as children and older adults, the health burden of respiratory morbidity was estimated using specific effect coefficients from previous studies conducted in UNT. Finally, we compared the health burden of respiratory morbidity before and after burning ban enforcement. Approximately 130,000 hospital visits for respiratory diseases were estimated to be attributable to fire-originated PM10 in UNT from 2014 to 2018. This estimation accounted for 1.3% of total hospital visits for respiratory diseases during the 5-year period, and 20% of those during burning events. Age-specific estimates revealed a larger impact of PM10 in the older adult group. The number of hospital visits for respiratory diseases attributable to fire-originated PM10 decreased from 1.8% to 0.5% after the burning ban policy was implemented in the area. Our findings suggest that PM10 released from vegetation fires is a health burden in UNT. The prohibition of the burning using regulatory measure had a positive impact on respiratory morbidity in this area.


Lateral flow dipstick test for genotyping of 15 beta-globin gene (HBB) mutations with naked-eye detection.
For definitive diagnosis of thalassemia carriers and patients, as well as for prenatal diagnosis, genotype analysis is of fundamental importance. We report a dry-reagent, lateral flow dipstick test that enables visual genotyping (detection by naked eye) of 15 mutations common in Mediterranean populations in the beta-globin gene (HBB). The method comprises 3 simple steps: (i) PCR amplification of a single 1896 bp segment of the beta globin gene flanking all 15 mutations; (ii) a multiplex (10-plex and/or 30-plex) primer extension reaction of the unpurified amplification product using allele-specific primers. Biotin is incorporated in the extended product; (iii) a dry-reagent multi-allele (10-plex) dipstick assay for visual detection of the primer extension reaction products within minutes. The total time required for PCR, primer extension reaction and the dipstick assay is ~2 h. The method was evaluated by genotyping 45 DNA samples of known genotypes and 54 blind samples. The results were fully concordant with reference methods. The method is simple, rapid, and cost-effective. Detection by the dipstick assay does not require specialized instrumentation or highly qualified personnel. The proposed method could be a particularly useful tool in laboratories with limited resources and a basis for point-of-care diagnostics especially in combination with PCR amplification from whole blood.


Find a pathway back into work.
Intensive condition management programmes are key to helping people claiming long-term sickness benefits get back into employment


Dawn of development: Exploring early human embryogenesis using stem cells.
Exploring the early stages of human embryonic development poses significant difficulties owing to ethical and technical limitations. Two recent studies in Nature report the self-organization of human stem cells into 3D embryoids that model features of the early post-implantation stages of human development.1,2.


Association between recurrent spontaneous abortions and circulating IgG antibodies to sperm tails in women.
The isotype and regional specificity of antisperm antibodies in the circulation of women with recurrent spontaneous abortions was examined. There was a statistically significant association (P less than 0.005) between the presence of IgG tail-directed antisperm antibodies and a history of unexplained recurrent spontaneous abortion. These antibodies were detected in 36.4% of 44 women with recurrent abortions and 14.6% of 616 female partners of infertile marriages. In contrast, no differences in IgG sperm head-directed antibodies or in IgA and IgM antisperm antibodies were observed between the two groups. Husbands of women in the miscarriage or infertile groups had similar semen evaluations. Antisperm antibodies may be a marker for defective immunosuppression in women with recurrent miscarriages. Alternatively, exposure of sperm-sensitized pregnant women to sperm may activate the maternal immune system to respond to paternal antigens present on the embryo.


Complete sequences of the ribosome recognition sites in vesicular stomatitis virus mRNAs: recognition by the 40S and 80S complexes.
Nucleotide sequences of the ribosome-protected translation initiation sites from the vesicular stomatitis virus (VSV) M and L protein mRNAs have been determined, completing the sequences of the sites from all the VSV mRNAs. A low level of protection at two internal AUG-containing sites in the N mRNA is also described. Small homologies are evident among some of the sites, but there are no obvious features common to all the sites other than a single AUG codon. In contrast, a large homology between the VSV M mRNA site and the alfalfa mosaic virus coat mRNA site (Koper-Zwarthoff et al., 1977) is noted. This homology suggests the existence of a common ancestral gene for these two apparently unrelated viruses. For each VSV mRNA species, the smallest sites protected in either the 40S or 80S initiation complexes are identical. These sites always contained the initiation codon, but only contained the capped 5' end in those mRNAs having the 5' end near the initiation site. If 40S ribosomes bind to the capped 5' end, either they do not protect it from nuclease digestion or the protection is only transitory in some VSV mRNAs. Consideration of the structures of the ribosome binding sites suggests that the differential effects of hypertonic shock on translation (Nuss and Koch, 1976) may be related to the distance between the 5' end of the mRNA and the initiation codon.


[A case of granulomatous rosacea coinciding with the use of etanercept: no relapse with infliximab].
A woman with psoriasis vulgaris and psoriatic arthritis developed granulomatous rosacea after four weeks of therapy with etanercept. When this agent was stopped, her skin lesions rapidly resolved with topical therapy, suggesting a causal relationship between the skin lesions and drug intake. To the best of our knowledge, this is the first report on rosacea as granulomatous cutaneous adverse drug reaction caused by etanercept. No relapse of skin changes appeared under extended and successful anti-psoriatic therapy with infliximab.


Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52 weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan.
Etelcalcetide is a second-generation calcimimetic for the management of secondary hyperparathyroidism (SHPT) in patients on dialysis. We performed a post-marketing surveillance (PMS) to obtain information on the safety and efficacy of etelcalcetide in clinical practice in Japan. This PMS enrolled SHPT patients who started initial treatment with etelcalcetide between April 1, 2017 and February 28, 2018 in Japan. Safety [adverse drug reactions (ADRs)] and efficacy [serum intact parathyroid hormone (iPTH), corrected calcium (cCa), phosphorous (P), and alkaline phosphatase (ALP)] were recorded for up to 52 weeks or until treatment discontinuation. Treatment decisions were at the physician's discretion. Of 1226 patients enrolled across 282 centers, safety and efficacy data were available for 1195 and 1192, respectively, while 933 continued treatment to Week 52. The starting dose was 5 mg in 82.0% of patients. There were 218 ADRs in 169 patients (14.1%). Metabolism and nutrition disorders (8.8%), adverse laboratory test results (1.8%), and gastrointestinal disorders (1.6%) were the most frequent classes of ADRs. Hypocalcemia-related ADRs occurred in 104 patients (8.7%). The percentage of patients with iPTH levels within the target range (60-240 pg/mL) steadily increased from 19.5% at Week 0 to 64.1% at Week 52 or last dose. cCa, P, and ALP levels remained well controlled. This was the first real-world, large-scale, long-term observational PMS of etelcalcetide in Japan. We did not observe any new safety concerns. Etelcalcetide was associated with clinically relevant improvements in serum iPTH and maintenance of serum cCa, P, and ALP levels.


Use of single percutaneous endoscopic gastrostomy in management of gastric volvulus in three patients.
Gastric volvulus is a rare condition that occurs when the stomach twists either in an organoaxial or mesenteroaxial direction. In patients with recurrent episodes of volvulus, standard therapy is surgical correction. Many patients, however, are not candidates for surgical therapy because of comorbid conditions or advanced age. Our aim was to determine if the insertion of a single percutaneous gastrostomy tube placement would assist in management of gastric volvulus in patients not able to undergo surgical therapy. The alpha-loop maneuver was used to reduce gastric volvulus in three elderly patients. A percutaneous endoscopic gastrostomy tube was then inserted to prevent recurrent volvulus. Single percutaneous gastrostomy tube placement was successful in managing volvulus in these three patients. Single percutaneous endoscopic gastrostomy tube placement is a useful treatment alternative to surgery in patients requiring therapy of gastric volvulus.


Lithium affects REM sleep occurrence, autonomic activity and brain second messengers in the rat.
The effects of a single intraperitoneal administration of lithium, a drug used to prevent the recurrence of mania in bipolar disorders, were determined in the rat by studying changes in: (i) the wake-sleep cycle; (ii) autonomic parameters (hypothalamic and tail temperature, heart rate); (iii) the capacity to accumulate cAMP and IP(3) in the preoptic-anterior hypothalamic region (PO-AH) and in the cerebral cortex (CC) under an hypoxic stimulation at normal laboratory and at low ambient temperature (T(a)). In the immediate hours following the injection, lithium induced: (i) a significant reduction in REM sleep; (ii) a non-significant reduction in the delta power density of the EEG in NREM sleep; (iii) a significant decrease in the concentration of cAMP in PO-AH at normal laboratory T(a); (iv) a significant increase of IP(3) concentration in CC following exposure to low T(a). The earliest and most sensitive effects of lithium appear to be those concerning sleep. These changes are concomitant with biochemical effects that, in spite of a systemic administration of the substance, may be differentiated according to the second messenger involved, the brain region and the ambient condition.


A glass menagerie of low complexity sequences.
Remarkably simple proteins play outsize roles in the execution of developmental complexity within biological systems. Sequence information determines structure and hence function, so how do low complexity sequences fulfill their functions? Recent discoveries are raising the curtain on a new dimension of the sequence-structure paradigm. In it, function derives not from the structures of individual proteins, but instead, from dynamic material properties of entire ensembles of the proteins acting in unison through phase changes. These phases include liquids, one-dimensional crystals, and - as elaborated herein - even glasses. The peculiar thermodynamics of glass-like protein assemblies, in particular, illuminate new principles of information flow through and, at times, orthogonal to the central dogma of molecular biology.


Comparative studies of unfolding and binding of ligands to human serum albumin in the presence of fatty acid: spectroscopic approach.
This study was undertaken to investigate the influence of fatty acid binding on the unfolding of HSA and how the fatty acid molecules can influence and/or compete with other ligand molecules bound to the protein. The equilibrium unfolding of fatted and fatty acid free HSA was measured by overlapping of unfolding transition curves monitored by different probes for secondary and tertiary structure and determining changes in free energy of unfolding. Proteins stability was studied by fluorescence spectroscopy, whereas conformational changes were detected by circular dichroism techniques. We have suggested a "molten globule" like intermediate state of HSA at a fairly high concentration of GnHCl (3.2 for fatty acid free and 3.6 for fatted). The free energy of stabilization (DeltaG(D)(H2O)) in the presence of fatty acid was found to be 900 cal mol(-1). We also analyze the effects of fatty acid on binding of ligands using spectroscopic technique and reported the equilibrium constants and free energies obtained from the binding and unfolding experiments.


Efficacy and safety of mycophenolate mofetil in progressive multiple sclerosis patients.
There are increasingly effective therapies for relapsing forms of multiple sclerosis (MS); however, the options for the progressive patient population are limited. The effect of mycophenolate mofetil (MMF), a disease-modifying agent for several autoimmune diseases, in progressive MS has not been explored effectively. We performed a prospective study to assess the safety and efficacy of MMF in progressive MS patients. We identified 64 patients enrolled in the comprehensive longitudinal database at the Partners MS Center, who fulfilled our inclusion criteria. They were exposed to MMF for at least 1 year with recorded clinical outcomes. Efficacy was assessed by comparing the absolute relapse rate (ARR), and the mean Expanded Disability Status Scale (EDSS) and timed 25 foot walk (T25FW) test scores before and after MMF treatment. At the start of MMF, 78% of patients (n = 50) were in the 4-7.5 EDSS range. There was a slight increase in mean EDSS from 5.49 ± 1.65 (n = 48) 1 year before MMF start to 5.85 ± 1.56 (n = 48) 1 year after (p = 0.020). The mean T25FW score increased 1 year before MMF from 12.3 ± 9.6 s (n = 38) to 15.6 ± 12.3 s (n = 38) 1 year after (p = 0.009). The ARR in the 2 years pre-MMF period was 0.30 ± 0.63, which decreased to a 0.09 ± 0.29 (p = 0.022) 2 years post MMF. MMF did not affect disease progression but did influence relapse rate. We believe that other medication options should be considered before MMF in advanced progressive patients.


Factors responsible for dermally induced epidermal hyperplasia.
The secondary epidermal hyperplasia seen over some dermal lesions can be experimentally induced in the guinea pig by the intracutaneous injection of carrageenan. This paper documents experiments directed to determining the factors that cause this epidermal reaction. Indomethacin, aspirin and polyphloretin phosphate were found to block the epidermal thickening. "Non inflammatory" stretching of the skin induced by a silastic implant caused an increase in the germinative population but no sustained epidermal hyperplasia. Rubbing into the skin a rubefacient cream produced more epidermal hyperplasia than did the base cream alone. It is suggested that the secondary epidermal hyperplasia from dermal abnormalities is multifactorial in its causation but that prostaglandin release might be involved and that increased blood flow may also play a role.


Counteracting MDM2-induced HIPK2 downregulation restores HIPK2/p53 apoptotic signaling in cancer cells.
Homeodomain-interacting protein kinase-2 (HIPK2) is a crucial regulator of p53 apoptotic function by phosphorylating serine 46 (Ser46) in response to DNA damage. In tumors with wild-type p53, its tumor suppressor function is often impaired by MDM2 overexpression that targets p53 for proteasomal degradation. Likewise, MDM2 targets HIPK2 for protein degradation impairing p53-apoptotic function. Here we report that zinc antagonised MDM2-induced HIPK2 degradation as well as p53 ubiquitination. The zinc inhibitory effect on MDM2 activity leads to HIPK2-induced p53Ser46 phosphorylation and p53 pro-apoptotic transcriptional activity. These results suggest that zinc derivatives are potential molecules to target the MDM2-induced HIPK2/p53 inhibition.


Radiation-Free Thoracic Endovascular Aneurysm Repair with Fiberoptic and Electromagnetic Guidance: A Phantom Study.
To evaluate the feasibility and accuracy of a radiation-free implantation of a thoracic aortic stent graft employing fiberoptic and electromagnetic tracking in an anthropomorphic phantom. An anthropomorphic phantom was manufactured based on computed tomography (CT) angiography data from a patient. An aortic stent graft application system was equipped with a fiber Bragg gratings and 3 electromagnetic sensors. The stent graft was navigated in the phantom by 3 interventionalists using the tracking data generated by both technologies. One implantation procedure was performed. The technical success of the procedure was evaluated using digital subtraction angiography and CT angiography (before and after the intervention). Tracking accuracy was determined at various anatomical landmarks based on separately acquired fluoroscopic images. The mean/maximum errors were measured for the stent graft application system and the tip/end of the stent graft. The procedure resulted in technical success with a mean error below 3 mm for the entire application system and <2 mm for the position of the tip of the stent graft. Navigation/implantation and handling of the device were rated sufficiently accurate and on par with comparable, routinely used stent graft application systems. The study demonstrates successful stent graft implantation during a thoracic endovascular aortic repair procedure employing advanced guidance techniques and avoiding fluoroscopic imaging. This is an essential step in facilitating the implantation of stent grafts and reducing the health risks associated with ionizing radiation during endovascular procedures.


Galactose-Grafted 2D Nanosheets from the Self-Assembly of Amphiphilic Janus Dendrimers for the Capture and Agglutination of Escherichia coli.
High aspect ratio, sugar-decorated 2D nanosheets are ideal candidates for the capture and agglutination of bacteria. Herein, the design and synthesis of two carbohydrate-based Janus amphiphiles that spontaneously self-assemble into high aspect ratio 2D sheets are reported. The unique structural features of the sheets include the extremely high aspect ratio and dense display of galactose on the surface. These structural characteristics allow the sheet to act as a supramolecular 2D platform for the capture and agglutination of E. coli through specific multivalent noncovalent interactions, which significantly reduces the mobility of the bacteria and leads to the inhibition of their proliferation. Our results suggest that the design strategy demonstrated here can be applied as a general approach for the crafting of biomolecule-decorated 2D nanosheets, which can perform as 2D platforms for their interaction with specific targets.


Virome and Inflammasomes, a Finely Tuned Balance with Important Consequences for the Host Health.
The virome is a network of viruses normally inhabiting humans. It forms a conspicuous portion of the so-called microbiome, once generically referred to as resident flora. Indeed, viruses infecting humans without leading to clinical disease are increasingly recognized as part of the microbiome and have an impact on the development of our immune system. In addition, they activate inflammasomes, multiprotein complexes that assemble in cells and that are responsible for the downstream effects of sensing pathogens. This review aims at summarizing the evidence on the role of the virome in modulating inflammation and emphasizes evidence for Anelloviruses as useful molecular markers to monitor inflammatory processes and immune system competence. We carried out a review of the literature published in the last 5 years and summarized older literature to take into account ground-breaking discoveries concerning inflammasome assembly and virome. A massive amount of data recently emerging demonstrate that the microbiome closely reflects what we eat, and many other unexpected variables. Composition, location, and amount of the microbiome have an impact on innate and adaptive immune defences. Viruses making up the virome contribute to shaping the immune system. Anelloviruses, the best known of such viruses, are present in most human beings, persistently without causing apparent disease. Depending on their interplay with such viruses, inflammasomes instruct host defences to tolerate or forfeit a specific microorganism. The virome plays an important role in shaping human immune defences and contributes to inflammatory processes by quenching or increasing them.


Inherited congenital normofunctional testicular hyperplasia and mental deficiency. A corroborative study.
Three 46,XY unrelated individuals out of 84 postpubertal male inpatients with severe mental deficiency in a psychiatric hospital were found to have megalorchidia and macrogenitosomia. One of the cases had a similarly affected brother. Endocrine studies were performed in two of the cases with similar results. Normal plasma levels of pituitary gonadotropins were found. A normal testicular function was demonstrated by the finding of normal: (a) baseline plasma testosterone levels and a significant rise following human chorionic gonadotropin administration, (b) sperm analysis, and (c) morphology and cell architecture of the testes. These results were compatible with normofunctional testicular hyperplasia confirming previous observations and allowing the definite individualization of a syndrome with mental deficiency probably due to an X-linked recessive mutation.


Decrease of the number of opioid receptors and of the responsiveness to morphineduring neuronal differentiation induced by 17beta-estradiol in estrogen receptor-transfected neuroblastoma cells (SK-ER3).
Estrogens modulate the density of opioid receptors in selected brain areas; however, it is not clear whether they exert such an effect directly on the cells which express the opioid receptors. Therefore, we analyzed the binding of [3H]-diprenorphine in human neuroblastoma cells stably transfected with the estrogen receptor cDNA (SK-ER3 cell line). A 16-hour exposure of these cells with 1 nM 17beta-estradiol induces a progressive morphological differentiation which appears clearly established 6 days after the suspension of the treatment. The binding of [3H]-diprenorphine was then measured immediately after the exposure to 17beta-estradiol (16 h) as well as 6 days later. The results shows that the number of opioid receptors in SK-ER3 cells is unaffected at 16 h but appears significantly reduced at 6 days. This effect is blocked by the estrogen antagonist ICI-182780, and is coincident to a decrease of the inhibitory effect of morphine on cyclic AMP accumulation. Binding experiments performed using selective ligands suggest that the micro subclass of opioid receptors is down-regulated by estradiol in SK-ER3 cells.


Identification and validation of the reference genes in the echiuran worm Urechis unicinctus based on transcriptome data.
Real-time quantitative PCR (RT-qPCR) is a crucial and widely used method for gene expression analysis. Selecting suitable reference genes is extremely important for the accuracy of RT-qPCR results. Commonly used reference genes are not always stable in various organisms or under different environmental conditions. With the increasing application of high-throughput sequencing, transcriptome analysis has become an effective method for identifying novel stable reference genes. In this study, we identified candidate reference genes based on transcriptome data covering embryos and larvae of early development, normal adult tissues, and the hindgut under sulfide stress using the coefficient of variation (CV) method in the echiuran Urechis unicinctus, resulting in 6834 (15.82%), 7110 (16.85%) and 13880 (35.87%) candidate reference genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the candidate reference genes were significantly enriched in cellular metabolic process, protein metabolic process and ribosome in early development and normal adult tissues as well as in cellular localization and endocytosis in the hindgut under sulfide stress. Subsequently, ten genes including five new candidate reference genes and five commonly used reference genes, were validated by RT-qPCR. The expression stability of the ten genes was analyzed using four methods (geNorm, NormFinder, BestKeeper, and ∆Ct). The comprehensive results indicated that the new candidate reference genes were more stable than most commonly used reference genes. The commonly used ACTB was the most unstable gene. The candidate reference genes STX12, EHMT1, and LYAG were the most stable genes in early development, normal adult tissues, and hindgut under sulfide stress, respectively. The log2(TPM) of the transcriptome data was significantly negatively correlated with the Ct values of RT-qPCR (Ct = - 0.5405 log2(TPM) + 34.51), which made it possible to estimate the Ct value before RT-qPCR using transcriptome data. Our study is the first to select reference genes for RT-qPCR from transcriptome data in Echiura and provides important information for future gene expression studies in U. unicinctus.


Expression of ZFX gene correlated with the central features of the neoplastic phenotype in human brain tumors with distinct phenotypes.
The zinc finger transcription factor zinc finger protein, X-linked (ZFX) acts as an important director of self-renewal in several stem cell types. Moreover, ZFX expression abnormally increases in various cancers and relates to tumor grade. We performed this study, to examine its role in the pathogenesis of astrocytoma and meningioma. We used real-time reverse transcription polymerase chain reaction method for evaluation of ZFX expression in 25 astrocytoma tumoral tissue and 25 meningioma tumoral tissues with different WHO grades. Furthermore, the association of gene expression with various clinic-pathological characteristics was examined. We found that there is a significant association between gene expression and different tumor grades, the presence or absence of invasion, forming and nonforming of glomeruloid vessels, the age over or under 50 and the presence or absence of calcification in astrocytomas. This is the first report that shows that ZFX was directly correlated with the central features of the neoplastic phenotype, including the growth of cancer cells, angiogenesis, and invasion. Regarding all the above-mentioned studies, it is highly plausible that silencing the expression of ZFX gene in gliomas has a major role in the therapeutic interventions of the disease in future.


Preliminary genetic linkage maps of Chinese herb Dendrobium nobile and D. moniliforme.
Dendrobium is an endangered genus in the orchid family with medicinal and horticultural value. Two preliminary genetic linkage maps were constructed using 90 F1 progeny individuals derived from an interspecific cross between D. nobile and D. moniliforme (both, 2n = 38), using random amplified polymorphic DNA (RAPD) and intersimple sequence repeat (ISSR). A total of 286 RAPD loci and 68 ISSR loci were identified and used for genetic linkage analysis. Maps were constructed by double pseudo-testcross mapping strategy using the software Mapmaker/EXP ver. 3.0, and Kosambi map distances were constructed using a LOD score greater than or equal to 4 and a recombination threshold of 0.4. The resulting frame map of D. nobile was 1474 cM in total length with 116 loci distributed in 15 linkage groups; and the D. moniliforme linkage map had 117 loci placed in 16 linkage groups spanning 1326.5 cM. Both maps showed 76.91% and 73.59% genome coverage for D. nobile and D. moniliforme, respectively. These primary maps provide an important basis for genetic studies and further medicinal and horticultural traits mapping and marker-assisted selection in Dendrobium breeding programmes.


A straightforward methodology for designing continuous monoclonal antibody capture multi-column chromatography processes.
A simple process development strategy for continuous capture multi-column chromatography (MCC) is described. The approach involves a few single column breakthrough experiments, based on several simplifying observations that enable users to rapidly convert batch processes into well-designed multi-column processes. The method was validated using a BioSMB(®) (Pall Life Sciences) lab scale multi-column system and a mAb capture process employing Protein A resin. The approach enables users to optimize MCC processes based on their internal preferences and constraints without requiring any mathematical modeling expertise.


2-[(3,3-Di-methyl-indolin-2-yl-idene)meth-yl]-4-[(3,3-dimethyl-3H-indol-1-ium-2-yl)methyl-idene]-3-oxo-cyclo-but-1-en-1-olate chloro-form disolvate.
In the title squaraine dye solvate, C26H24N2O2·2CHCl3, the dye mol-ecule is essentially planar, except for the methyl groups, having a maximum deviation over the 26-membered delocalized bond system of 0.060 (2) Å. It possesses crystallographic twofold rotational symmetry with the indole ring systems adopting a syn conformation. The mol-ecular structure features intra-molecular N-H⋯O hydrogen bonds enclosing conjoint S7 ring motifs about one of the dioxo-cyclo-butene O atoms, while the two chloro-form solvent mol-ecules are linked to the second O atom through C-H⋯O hydrogen bonds.


Substitution of flavored cigarillos with menthol cigarettes among young adults in the U.S.
Young adult cigarillo users often cite flavor as a primary reason for initiating and sustaining product use and are more likely to concurrently use other tobacco products such as menthol cigarettes. This study examines substitution with menthol cigarettes among cigarillo users facing a hypothetical ban on flavored cigarillos. Current young adult (21-28 years) cigarillo users were recruited from October 2020 to April 2021 for an online survey about cigarillo and other tobacco use behaviors. Participants (n = 500) self-reported past or current menthol cigarette experience, and if they would switch to menthol cigarettes if they could not get flavored cigarillos. Logistic regression was used to test differences in switching behaviors by level of experience with menthol cigarettes. Most young adult cigarillo users (76.8 %) had ever used a menthol cigarette and 46.6 % reported current use of menthol cigarettes. No participant who had never used menthol cigarettes reported they would switch to menthol cigarettes. Current users were 4.2 times as likely to say they would switch after controlling for demographic characteristics and nicotine dependence. Most young adult cigarillo users reported they would not switch to menthol cigarettes if flavored cigarillos became unavailable. However, participants who currently use or have used menthol cigarettes were more likely to report their intention to switch products than those who had never used menthol cigarettes. There may be a subsequent increase in menthol cigarette use among past menthol cigarette users if policies restricting flavored tobacco products exclude menthol cigarettes, diluting these policies' intended population health impact.


Good practice for publishing the results of clinical trials.
Publication is an important stage in the research process, yet until recently few guidelines existed about how trials should be published. This article reviews recent developments such as Good Publication Practice for pharmaceutical companies and recommendations from medical editors, medical writers and the pharmaceutical industry which encourage responsible practices and greater transparency.


Differential effect of the calmodulin inhibitor trifluoperazine in modulating cellular accumulation, retention and cytotoxicity of doxorubicin in progressively doxorubicin-resistant L1210 mouse leukemia cells. Lack of correlation between cellular doxorubicin levels and expression of resistance.
Calmodulin inhibitors are effective in enhancing cytotoxic effects of doxorubicin (DOX) in DOX-resistant cells, possibly by enhancing cellular levels of drug. In the present study, L1210 mouse leukemia cells adapted to grow in vitro, in the presence of 0.025 to 0.25 microgram/ml DOX, and identified as L1210/DOX0.025, L1210/DOX0.05, L1210/DOX0.1, and L1210/DOX0.25 were approximately 5-, 10-, 20-, and 40-fold DOX resistant, respectively, compared to parent-sensitive cells (L1210/S). Using a soft agar colony assay and 3-hr drug exposure, the IC50 concentration of DOX in the progressively DOX-resistant (5- to 40-fold) L1210 cells ranged from 0.25 to 2.0 micrograms/ml and from 0.08 to 0.25 microgram/ml in the absence and presence of a non-cytotoxic concentration of 5 microM trifluoperazine (TFP) respectively. Further, based on the observed in vitro cytotoxic response, the IC50 concentration of DOX in the presence of 5 microM TFP was 2.5-, 4-, 6.7- and 8-fold lower than DOX without 5 microM TFP in the L1210/DOX0.025, L1210/DOX0.05, L1210/DOX0.1, and L1210/DOX0.25 resistant sublines respectively. In contrast, the IC50 of DOX in L1210/S cells was approximately 0.05 microgram/ml with or without 5 microM TFP. Cellular accumulation of DOX was 15-50% lower in the progressively resistant L1210 sublines compared to similarly treated L1210/S cells. However, in the presence of 5 microM TFP, cellular accumulation of DOX in the L1210/DOX0.05 and L1210/DOX0.1 but not L1210/DOX0.25 was comparable to the L1210/S cells. Cellular retention of DOX in the absence or presence of 5 microM TFP was comparable in similarly treated L1210/S, L1210/DOX0.05 and L1210/DOX0.1 cells, and a 2-fold reduction in the retention of DOX in the absence versus the presence of 5 microM TFP was apparent only in L1210/DOX0.25 cells. At the IC50 of DOX in the presence of 5 microM TFP, although cellular accumulation of DOX was concentration dependent over the range of 1-20 microM TFP, enhancement in cytotoxicity of DOX was dose dependent at 1-5 microM TFP but not 5-20 microM TFP. In cells treated for 3 hr at the IC50 concentration of DOX alone or DOX plus 5 microM TFP, cellular accumulation of DOX was 7- to 14-fold and 2.5- to 3.5-fold higher, respectively, in resistant than in sensitive cells. Additionally, following treatment for 3 hr at the IC50 dose of DOX in the absence or presence of 5 microM TFP, drug retention at 3 hr was 4- to 6-fold and 1.5-fold higher, respectively, in the resistant versus sensitive cells.(ABSTRACT TRUNCATED AT 400 WORDS)


Student performance in medical biochemistry and genetics: comparing campus-based versus zoom-based lecture delivery.
We appraised the effectiveness of online (Zoom) delivery versus live campus-based delivery of lectures in biochemistry and genetics courses and assessed the security of remote versus campus-administered exams. Participants were 601 students entering Michigan State University College of Osteopathic Medicine in 2019 or 2020. The former cohort completed courses and exams on campus, while the latter completed courses online due to the COVID-19 pandemic. For the biochemistry and genetics courses, the same lecturers delivered the same content and used identical exam questions for assessments in 2019 and 2020. The investigators compared percent correct for each question in 2019 and 2020. This study found 84 of 126 (67%) of the questions yielded little difference (3% or less in % correct) between live delivery and Zoom delivery. For questions whose % correct index differed by 4% or more, Zoom delivery yielded a better performance for 16 questions (13%), while 19 questions (15%) showed live lectures performed better. Seven of the questions (6%) had an identical mode of delivery in 2019 and 2020 (e.g., self-study exercise). These served as "control questions" for which equivalent student performance was expected. The 126 questions analyzed spanned a wide range in the % correct index, from 60% correct to > 90% correct. The results suggest that Zoom and on-campus delivery of the content in biochemistry and genetics yielded similar achievement of course objectives. The high concordance, between 2019 and 2020, of the % correct for individual questions also speaks to exam security including online proctoring.


Kinetics of cytokine expression in cirrhotic rats.
Cytokines are involved in liver injury and cirrhosis and systemic and hepatic cytokine levels may help predict cirrhosis evolution. However, the relevant survey has not been performed. Male Sprague-Dawley rats (240-270 g) received either common bile duct ligation (BDL, animal model of cholestatic liver injury) or sham operation (control). Five rats were sacrificed and liver and serum were collected from each in weeks 1, 2, 4, 6, 8 and 10 after surgery. Hepatic expression of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were analyzed by immunohistochemial staining. The corresponding serum levels were measured by ELISA. Compared to the corresponding sham groups, hepatic expression of these cytokines in BDL rats was significantly and progressively enhanced during cirrhosis development. However, serum IFN-γ levels of BDL rats did not change significantly. Serum TNF-α of BDL rats increased gradually and reached a peak in week 6. Serum TGF-β level was elevated up to week 8, whereas IL-10 level decreased progressively until week 6. Cirrhosis development in BDL rats is associated with progressively enhanced expression of hepatic pro-inflammatory and anti-inflammatory cytokines, which is not in accord with the corresponding serum concentration. The circulating cytokine concentration may not totally reflect the hepatic expression level throughout the development of cirrhosis.


Can a visual representation support the online control of memory-dependent reaching? Evident from a variable spatial mapping paradigm.
We investigated whether a representation of a visual target can be stored in memory and used to support the online control of reaching movements. To distinguish between the use of a stored target representation for movement planning versus online control, we employed a novel movement environment in which participants could not fully plan their action in advance of movement initiation; that is, the spatial mapping between the movement of a computer mouse and the on-screen movement of a cursor was randomly varied from trial to trial. As such, participants were required to use online control to reach the target position. Reaches were examined in full-vision and three memory-dependent conditions (0, 2, and 5 s of delay). Absolute constant error did not accumulate between full-vision and brief delay trials (i.e., the 0-s delay), suggesting a stored representation of the visual target can be used for online control of reaching given a sufficiently brief delay interval. Longer delay trials (2 and 5 s) were less accurate and more variable than brief delay trials; however, the residual accuracy of these memory-dependent actions suggests that the motor system may have access to a stored representation of the visual target for online control processes for upwards of 5 s following target occlusion.


[Determinants and patterns of bicycle use and traffic accidents among bicycling workers in Pelotas, Rio Grande do Sul, Brazil].
A population-based cross-sectional study was conducted in Pelotas, southern Brazil, focusing on the determinants and patterns of bicycle use as a mode of commuting by workers. Accidents during commuting and use of safety equipment were also studied. The sample included 1,705 workers (> 15 years of age) living in the urban area of Pelotas and using various modes of transportation during commuting. Crude and adjusted analyses were performed using Poisson regression, taking the design effect into account. Prevalence of bicycle use was 17.2% (95%CI: 15.4%-19.0%). Male workers and those with low schooling and low income presented higher prevalence. Less than 1.0% of the bicycles featured the safety equipment required by the Brazilian Traffic Code, and 15.0% did not even have brakes. Nearly 6.0% of workers who commuted by bicycle had suffered accidents resulting in injuries during the previous 12 months. The authors conclude that bicycling workers are a priority for interventions aimed at reducing traffic accidents.


Antibodies directed against synthetic peptides distinguish between the catalytic subunits of protein phosphatases 1 and 2A.
Two antipeptide antibodies (designated type 1 antibody and type 2A antibody) were raised against synthetic peptides, Cys-Thr-Pro-Pro-Arg-Asn-Ser-Ala-Lys-Ala-Lys-Lys and Cys-Val-Thr-Arg-Arg-Thr-Pro-Asp-Try-Phe-Leu, corresponding to the carboxyl termini of the catalytic subunits of protein phosphatase 1 and phosphatase 2A (Cys was added for specific coupling to carrier protein). These antipeptide antibodies were highly specific and were useful in discriminating between protein phosphatase 1 and phosphatase 2A in crude extracts or purified preparations. Type 2A antibody reacted with both native and denatured protein phosphatase 2A whereas under the same condition type 1 antibody reacted only with denatured protein phosphatase 1.


Lateral diffusion of wheat germ agglutinin-labeled glycoconjugates in the membrane of differentiating HL-60 and U-937 cells assessed with fluorescence recovery after photobleaching (FRAP).
The promyelocytic leukemia cell line HL-60 and the histiocytic cell line U-937 were grown in suspension culture. They were induced to differentiate during 5-d cultivation in the presence of dimethylsulfoxide (DMSO; 1.3% w/v) or phorbol-12-myristate-acetate (PMA; 10(-7) M), which yields granulocyte- and macrophage-like cells, respectively. Differentiation was evidenced by increased capacity to recognize and phagocytize IgG- or complement-coated yeast particles. Aliquots taken from the cultures with and without DMSO (or PMA) were spun down directly on glass microscope slides, washed, labeled with fluoresceinated wheat germ agglutinin (WGA), and directly examined at room temperature for the rate of fluorescence recovery after photobleaching (FRAP). It was found that cultivation of the HL-60 and the U-937 cells in the presence of DMSO, which yields granulocyte-like cells, reduced the average value of lateral diffusion coefficient D (X 10(10] from 1.72 +/- 0.13 cm2s-1 to 0.97 +/- 0.13 cm2s-1 and from 1.77 +/- 0.11 cm2s-1 to 0.82 +/- 0.13 cm2s-1, respectively. U-937 cells grown with PMA also showed a reduction of D(X 10(10] to 0.88 +/- 0.10 cm2s-1. There was a larger immobile fraction of fluorescence in the HL-60 cells than in the U-937 cells, viz., 70-80% compared to 10-50%. The total number of binding sites for WGA was not altered, but the surface density changed, since the HL-60 and the U-937 cells became smaller and larger, respectively, when grown in the presence of DMSO. It is concluded that differentiation reduces the average lateral mobility of the WGA-binding membrane component by a factor around 2.


Arthroscopic Conjoint Tendon Transfer: A Technique for Revision Anterior Shoulder Stabilization.
Revision anterior stabilization of the shoulder presents a challenge to the surgeon and carries a higher risk of recurrent dislocation than primary repair. The Latarjet procedure may be more reliable than revision soft-tissue repair but may not be indicated in patients without significant glenoid bone loss. We describe an arthroscopic technique of conjoint tendon transfer using a combination of suspensory and interference screw fixation for patients without significant glenoid bone loss (<15%). The arthroscopic approach to this procedure allows intra-articular visualization to assist in mobilization of the conjoint tendon, accurate bone tunnel placement, and subsequent labral repair. It avoids the additional steps of bone block preparation and the larger portals required for arthroscopic Latarjet techniques, in addition to eliminating potential complications due to coracoid bone block resorption.


Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase: PASL vs DSC-MRI.
Non-invasive pulsed arterial spin labeling (PASL) MRI is a method to study brain perfusion that does not require the administration of a contrast agent, which makes it a valuable diagnostic tool as it reduces cost and side effects. The purpose of the present study was to establish the viability of PASL as an alternative to dynamic susceptibility contrast (DSC-MRI) and other perfusion imaging methods in characterizing changes in perfusion patterns caused by seizures in epileptic patients. We evaluated 19 patients with PASL. Of these, the 9 affected by high-frequency seizures were observed during the peri-ictal period (within 5hours since the last seizure), while the 10 patients affected by low-frequency seizures were observed in the post-ictal period. For comparison, 17/19 patients were also evaluated with DSC-MRI and CBF/CBV. PASL imaging showed focal vascular changes, which allowed the classification of patients in three categories: 8 patients characterized by increased perfusion, 4 patients with normal perfusion and 7 patients with decreased perfusion. PASL perfusion imaging findings were comparable to those obtained by DSC-MRI. Since PASL is a) sensitive to vascular alterations induced by epileptic seizures, b) comparable to DSC-MRI for detecting perfusion asymmetries, c) potentially capable of detecting time-related perfusion changes, it can be recommended for repeated evaluations, to identify the epileptic focus, and in follow-up and/or therapy-response assessment.


The effect of river damming on vegetation: is it always unfavourable? A case study from the River Tiber (Italy).
River damming leads to strong hydromorphological alterations of the watercourse, consequently affecting river vegetation pattern. A multitemporal and spatial analysis of the dam effect on composition, structure and dynamic of the upstream vegetation was performed on Tiber River at Nazzano-dam (Rome). The main research questions were as follows: How does plant landscape vary over time and along the river? Where does the dam effect on vegetation end? How does naturalistic importance of the vegetation affected by damming change over time? Data collection was performed mapping the vegetation in aerial photos related to the period before (1944), during (1954) and after dam construction (1984, 2000). The plant landscape has significantly changed over time and along the river, particularly as a result of the dam construction (1953). The major vegetation changes have involved riparian forests and macrophytes. Dam effect on vegetation is evident up to 3 km, and gradually decreases along an attenuation zone for about another 3 km. Despite the fact that the damming has caused strong local hydromorphological modification of the river ecosystem transforming it into a sub-lacustrine habitat, it has also led to the formation of wetlands of considerable naturalistic importance. Indeed, in these man-made wetlands, optimal hydrological conditions have been created by favouring both the expansion of pre-existing riparian communities and the rooting of new aquatic communities, albeit typical of lacustrine ecosystems. Some of these plant communities have become an important food resource, refuge or nesting habitats for aquatic fauna, while others fall into category of Natura 2000 habitats. Therefore, river damming seems to have indirectly had a "favourable" effect for habitat conservation and local biodiversity.