Analog of astrophysical magnetorotational instability in a Couette-Taylor flow of polymer fluids.
We report experimental observation of an instability in a Couette-Taylor flow of a polymer fluid in a thin gap between two coaxially rotating cylinders in a regime where their angular velocity decreases with the radius while the specific angular momentum increases with the radius. In the considered regime, neither the inertial Rayleigh instability nor the purely elastic instability is possible. We propose that the observed "elastorotational" instability is an analog of the magnetorotational instability which plays a fundamental role in astrophysical Keplerian accretion disks.


[Pulmonary arterial hypertension: modern diagnostics and therapy--Part 1].
Pulmonary arterial hypertension (PAH) belongs to the group of rare diseases and the morbidity rate is 15 to 50 people per million per year. Before the era of specific treatment of PAH, the prognosis was poor. The average life expectancy of the patients was 2.8 years. However, in the last years there has been a breakthrough in treating the patients with PAH. The introduction of this specific treatment has prolonged the life and improved the quality of it within the group of the patients with PAH. In Poland, since 2008 the therapy has been organized by the Pulmonary Hypertension Therapeutic Program. PAH is a recognition done by excluding more probable causes of pulmonary hypertension (PH) such as: PH due to left heart disease and lung disease, chronic thromboembolic pulmonary hypertension (CTEPH) and PH with multifactorial mechanisms. The clinical symptoms of pulmonary hypertension are non-specific, they develop for a several months and they are mainly caused by progressive right ventricular failure. The base of PAH recognition is echocardiography, which indirectly estimates the pulmonary artery systolic pressure. However, the golden standard of PAH diagnostics is right heart catheterization (RHC) with measurements of pulmonary arterial pressure (PAP), right atrial pressure (RAP), right ventricular pressure and pulmonary wedge pressure (PWP). The early PAH recognition and the correct classification of patients to the treatment organized by the Pulmonary Hypertension Therapeutic Program give them a chance for longer and more comfortable life.


Weekend warrior physical activity pattern and common mental disorder: a population wide study of 108,011 British adults.
The dose-response association between physical activity (PA) and mental health is poorly described. We explored cross-sectional associations between physical activity and common mental disorder (psychological distress) in 'weekend warriors' who do all their exercise in one or two sessions per week. Adult participants (n = 108,011, age = 47 ± 17 yrs., 46.5% men) were recruited from general population household-based surveys (Health Survey for England and Scottish Health Survey) from 1994 to 2004. Data were pooled and analyzed using logistic regression models. Moderate to vigorous physical activity (MVPA) was self-reported and psychological distress was measured using the 12 item General Health Questionnaire (GHQ-12). Psychological distress (GHQ-12 > 3) was prevalent in 14.5% of the sample. In healthy participants an inverse association between PA and psychological distress was optimal at the PA guideline (150 mins/wk. MVPA or 75 min/wk. Vigorous PA) regardless of whether it was accumulated in one or two bouts per week "Weekend warrior" (odd ratio = 0.68, 95% CI, 0.63, 0.73) or as more frequent daily bouts (odd ratio = 0.68, 95% CI, 0.64, 0.72) in comparison to the inactive reference group. In participants with chronic health conditions an inverse association between PA and psychological distress was also evident at lower doses (one or two sessions of PA a week below PA guideline) (OR = 0.72, 95% CI, 0.68, 0.77). Undertaking vigorous intensity PA as part of the PA guideline conferred additional benefit in women (odds ratio = 0.87, 95% CI, 0.75, 1.00), but not men. Mental health benefits may be accrued through different PA patterns, thus individual approaches to prescribing exercise should be promoted.


Observation of the disorder-induced crystal-to-glass transition.
The role of frustration and quenched disorder in driving the transformation of a crystal into a glass is investigated in quasi-two-dimensional binary colloidal suspensions. Frustration is induced by added smaller particles. The crystal-glass transition is measured to differ from the liquid-glass transition in quantitative and qualitative ways. The crystal-glass transition bears structural signatures similar to those of the crystal-fluid transition: at the transition point, the persistence of orientational order decreases sharply from quasilong range to short range, and the orientational order susceptibility exhibits a maximum. The crystal-glass transition also features a sharp variation in particle dynamics: at the transition point, dynamic heterogeneity grows rapidly, and a dynamic correlation length scale increases abruptly.


Quantitative Assessment of Optimal Bone Marrow Site for the Isolation of Porcine Mesenchymal Stem Cells.
Background. One of the most plentiful sources for MSCs is the bone marrow; however, it is unknown whether MSC yield differs among different bone marrow sites. In this study, we quantified cellular yield and evaluated resident MSC population from five bone marrow sites in the porcine model. In addition, we assessed the feasibility of a commercially available platelet concentrator (Magellan® MAR01™ Arteriocyte Medical Systems, Hopkinton, MA) as a bedside stem cell concentration device. Methods. Analyses of bone marrow aspirate (BMA) and concentrated bone marrow aspirate (cBMA) included bone marrow volume, platelet and nucleated cell yield, colony-forming unit fibroblast (CFU-F) number, flow cytometry, and assessment of differentiation potential. Results. Following processing, the concentration of platelets and nucleated cells significantly increased but was not significantly different between sites. The iliac crest had significantly less bone marrow volume; however, it yielded significantly more CFUs compared to the other bone marrow sites. Culture-expanded cells from all tested sites expressed high levels of MSC surface markers and demonstrated adipogenic and osteogenic differentiation potential. Conclusions. All anatomical bone marrow sites contained MSCs, but the iliac crest was the most abundant source of MSCs. Additionally, the Magellan can function effectively as a bedside stem cell concentrator.


Does therapeutic electrical stimulation improve function in children with disabilities? A comprehensive literature review.
The use of therapeutic electrical stimulation for medical purposes is not new; it has been described in medical textbooks since the 18th century, but its use has been limited due to concerns for tolerance and lack of research showing efficacy. The purpose of this review is to discuss the potential clinical applicability, while clarifying the differences in electrical stimulation (ES) treatments and the theory behind potential benefits to remediate functional impairments in youth.The literature review was performed as follows: A total of 37 articles were reviewed and the evidence for use in pediatric diagnoses is reported.The synthesis of the literature suggests that improvements in various impairments may be possible with the integration of ES. Most studies were completed on children with cerebral palsy (CP). Electrical stimulation may improve muscle mass and strength, spasticity, passive range of motion (PROM), upper extremity function, walking speed, and positioning of the foot and ankle kinematics during walking. Sitting posture and static/dynamic sitting balance may be improved with ES to trunk musculature. Bone mineral density may be positively affected with the use of Functional Electrical Stimulation (FES) ergometry. ES may also be useful in the management of urinary tract dysfunction and chronic constipation. Among all reviewed studies, reports of direct adverse reactions to electrical stimulation were rare.In conclusion, NMES and FES appear to be safe and well tolerated in children with various disabilities. It is suggested that physiatrists and other healthcare providers better understand the indications and parameters in order to utilize these tools effectively in the pediatric population. MeSH terms: Electrical stimulation; child; review.


A qualitative study of rural healthcare providers' views of social, cultural, and programmatic barriers to healthcare access.
Ensuring access to healthcare is a complex, multi-dimensional health challenge. Since the inception of the coronavirus pandemic, this challenge is more pressing. Some dimensions of access are difficult to quantify, namely characteristics that influence healthcare services to be both acceptable and appropriate. These link to a patient's acceptance of services that they are to receive and ensuring appropriate fit between services and a patient's specific healthcare needs. These dimensions of access are particularly evident in rural health systems where additional structural barriers make accessing healthcare more difficult. Thus, it is important to examine healthcare access barriers in rural-specific areas to understand their origin and implications for resolution. We used qualitative methods and a convenience sample of healthcare providers who currently practice in the rural US state of Montana. Our sample included 12 healthcare providers from diverse training backgrounds and specialties. All were decision-makers in the development or revision of patients' treatment plans. Semi-structured interviews and content analysis were used to explore barriers-appropriateness and acceptability-to healthcare access in their patient populations. Our analysis was both deductive and inductive and focused on three analytic domains: cultural considerations, patient-provider communication, and provider-provider communication. Member checks ensured credibility and trustworthiness of our findings. Five key themes emerged from analysis: 1) a friction exists between aspects of patients' rural identities and healthcare systems; 2) facilitating access to healthcare requires application of and respect for cultural differences; 3) communication between healthcare providers is systematically fragmented; 4) time and resource constraints disproportionately harm rural health systems; and 5) profits are prioritized over addressing barriers to healthcare access in the US. Inadequate access to healthcare is an issue in the US, particularly in rural areas. Rural healthcare consumers compose a hard-to-reach patient population. Too few providers exist to meet population health needs, and fragmented communication impairs rural health systems' ability to function. These issues exacerbate the difficulty of ensuring acceptable and appropriate delivery of healthcare services, which compound all other barriers to healthcare access for rural residents. Each dimension of access must be monitored to improve patient experiences and outcomes for rural Americans.


Advances in Transition-Metal-Catalysed Alkyne Hydroarylations.
We present herein a personal account of our achievements in the development of novel catalytic systems based on late-transition-metal complexes for the hydroarylation of alkynes. In particular, our targets were intermolecular hydroarylation reactions with arene or heteroarene substrates devoid of directing groups. We have shown that complexes of palladium, platinum or gold with N-heterocyclic carbene (NHC) ligands can be particularly useful catalysts for this reaction; the NHC ligand imparts greater stability to the complex and renders the catalytic system more productive. Furthermore, we have identified promoters and reaction media that allow to significantly improve the catalytic activity under mild conditions, to control the reaction chemoselectivity and to steer it towards more complex products; thus making this reaction considerably more attractive for the synthetic chemist.


Fourier transform microwave spectroscopy of the Rg-SH(2Pi(i)) complexes (Rg:Ne, Kr): determination of the intermolecular potential energy surfaces.
Pure rotational spectra of Ne-SH and Kr-SH have been studied by Fourier transform microwave spectroscopy. R-branch transitions in the lower-spin component (Omega=3/2) corresponding to a linear (2)Pi(i) radical were observed for J(")=1.5-4.5 in the region 11-25 GHz for Ne-SH and for J(")=1.5-6.5 in the region 5-20 GHz for Kr-SH, respectively, with parity doublings and hyperfine splittings associated with the H nucleus. Although the spectral pattern of Kr-SH is relatively regular, that of Ne-SH is irregular with the J dependence of the parity doublings quite different from other Rg-SH or Ar-OH complexes. Two-dimensional intermolecular potential energy surfaces (IPSs) for both of the species have been determined from the least-squares fittings of the observed rotational transitions utilizing results of high-level ab initio calculations. These IPSs reproduce the observed transition frequencies within the experimental error and provide accurate knowledge on the intermolecular interaction and internal dynamics. Systematic comparisons of Rg-SH complexes have clarified various features of this series of complexes.


Sinomenine exerts antitumour effect in gastric cancer cells via enhancement of miR-204 expression.
Gastric carcinoma (GC) is a pernicious neoplasm with high morbidity and mortality. Sinomenine (SIN) has long been exploited to heal rheumatoid arthritis. Recently, SIN has been discovered to exert the antitumour functions in diverse cancers. However, the impacts of SIN on GC remain indistinct. We attempted to expose the antitumour effect of SIN on GC. MKN45 and SGC-7901 cells were administered with SIN for 24 hours, cell viability, proliferation, apoptosis, migration, invasion and the associated proteins in the above processes were examined via exploiting CCK-8, BrdU, flow cytometry, Transwell and Western blot. MiR-204 expression in GC tumour tissues, different GC cell lines and SIN-stimulated GC cells was investigated by executing RT-qPCR. The above cell biological processes were reassessed after transfection with miR-204 inhibitor. The latent mechanisms were probed by examining AMPK and Wnt/β-catenin pathways. We found that SIN memorably repressed cell proliferation, evoked apoptosis and affected CyclinD1, Bcl-2, Bax and cleaved-caspase-3 expression in MKN45 and SGC-7901 cells. Cell migration, invasion and expression of MMP-9 and Vimentin were all restrained by SIN stimulation. The increase of miR-204 was discovered in GC tissues and SIN-treated MKN45 and SGC-7901 cells. But suppression of miR-204 was observed in AGS, MKN28, MKN45 and SGC-7901 cells. Suppression of miR-204 overturned the inhibitory functions of SIN in MKN45 and SGC-7901 cells. Besides, SIN prohibited AMPK and Wnt/β-catenin pathways via enhancement of miR-204. In conclusion, these findings suggested that SIN exerted the antitumour activity in GC cells by hindering AMPK and Wnt/β-catenin pathways via enhancement of miR-204.


Selecting candidates for radical prostatectomy.
Men with clinically localized prostate cancer and their physicians are faced with the management decision of radical prostatectomy, radiation therapy, or watchful waiting. Who is the best candidate for radical prostatectomy? Is cure the only relevant outcomes parameter? Does age make a difference? Are imaging studies necessary? This review provides answers, step-by-step, in the decision-making process.


Development and validation of a robust capillary electrophoresis method for impurity profiling of etomidate including the determination of chiral purity using a dual cyclodextrin system.
An enantioselective CE assay for the simultaneous determination of the enantiomeric purity and of related substances of etomidate has been developed and validated using a binary chiral selector system employing 30 mg/mL beta-CD and 4.6 mg/mL sulfated-beta-CD in a 150 mM potassium phosphate buffer, pH 2.1. The method was validated with respect to specificity, range, linearity, LOQ and LOD, precision and accuracy. The assay allowed the detection and determination of related substances including (S)-etomidate at the 0.05% w/w level, the reporting threshold as defined by the International Conference on Harmonisation guidelines as well as the European Pharmacopoeia. Robustness testing was carried out by an "Augmented Plackett-Burman" design. Quantitation of the compounds was performed by calibration graphs with respect to lidocaine hydrochloride as internal standard and by peak area normalization, the procedure usually applied by pharmacopoeias. Although data obtained from the calibration graphs constructed with the aid of the internal standard were more accurate based on compound recovery, peak area normalization may also be used without significant loss of accuracy and precision.


Histochemical identification of the striated muscle of the canine esophagus.
Histochemistry on the cervical, thoracic, and abdominal esophageal muscle of immature, young, and adult normal dogs revealed type IIA striated musculature in contrast to some other species. No other types or subtypes were observed. This suggests that esophageal muscle type is established at birth and does not vary or that any variation has been completed by 4 weeks-of-age unlike some canine limb musculature.


Effect of diffusion constant on the morphology of dendrite growth in lithium metal batteries.
Lithium dendrites can lead to a short circuit and battery failure, and developing strategies for their suppression is of considerable importance. In this work, we study the growth of dendrites in a simple model system where the solvent is a continuum and the lithium ions are hard spheres that can deposit by sticking to existing spheres or the electrode surface. Using stochastic dynamics simulations, we investigate the effect of applied voltage and diffusion constant on the growth of dendrites. We find that the diffusion constant is the most significant factor, and the inhomogeneity of the electric field does not play a significant role. The growth is most pronounced when the applied voltage and diffusion constant are both low. We observe a structural change from broccoli to cauliflower shape as the diffusion constant is increased. The simulations suggest that a control of electrolyte parameters that impact lithium diffusion might be an attractive route to controlling dendrite growth.


The Relationship between Markers of Inflammation and Degeneration in the Central Nervous System and the Blood-Brain Barrier Impairment in Alzheimer's Disease.
It is known that YKL-40- a marker of glial inflammation, and VILIP-1- a marker of neuronal injury, reflect functional and structural changes in AD brains, although there is limited data concerning their potential influence on blood-brain barrier (BBB) homeostasis. Therefore, the aim of our study was to investigate the relationship between markers of inflammation and degeneration in the central nervous system (CNS) of patients with AD and mild cognitive impairment (MCI) as well as immunological response in CNS and BBB function. Cerebrospinal fluid (CSF) concentrations of proteins tested were determined in 45 AD patients, 18 MCI subjects, and 23 non-demented controls using ELISA method. CSF concentrations of YKL-40 were significantly higher in MCI and AD patients, whereas CSF levels of VILIP-1 were statistically higher in the AD group as compared to the subjects without cognitive deficits. Elevated concentrations of YKL-40 correlated significantly with increased albumin quotient and decreased Aβ42/40 ratio in AD patients and with IgG quotient in the total study group. We did not find a relationship between VILIP-1 and immunological parameters reflecting BBB dysfunction and humoral immune response. Our findings indicate that YKL-40 may contribute to decreased stability and increased permeability of BBB in AD patients. It is assumed that YKL-40 is implicated in the development of brain barriers, although its precise mechanism of action in the BBB disruption remains unrevealed. Further studies on larger groups of patients are required to confirm our hypothesis.


Molecular interactions of Epstein-Barr virus capsid proteins.
The capsids of herpesviruses, which comprise major and minor capsid proteins, have a common icosahedral structure with 162 capsomers. An electron microscopic study shows that Epstein-Barr virus (EBV) capsids in the nucleus are immunolabeled by anti-BDLF1 and anti-BORF1 antibodies, indicating that BDLF1 and BORF1 are the minor capsid proteins of EBV. Cross-linking and electrophoresis studies of purified BDLF1 and BORF1 revealed that these two proteins form a triplex that is similar to that formed by the minor capsid proteins, VP19C and VP23, of herpes simplex virus type 1 (HSV-1). Although the interaction between VP23, a homolog of BDLF1, and the major capsid protein VP5 could not be verified biochemically in earlier studies, the interaction between BDLF1 and the EBV major capsid protein, viral capsid antigen (VCA), can be confirmed by glutathione S-transferase (GST) pulldown assay and coimmunoprecipitation. Additionally, in HSV-1, VP5 interacts with only the middle region of VP19C; in EBV, VCA interacts with both the N-terminal and middle regions of BORF1, a homolog of VP19C, revealing that the proteins in the EBV triplex interact with the major capsid protein differently from those in HSV-1. A GST pulldown study also identifies the oligomerization domains in VCA and the dimerization domain in BDLF1. The results presented herein reveal how the EBV capsid proteins interact and thereby improve our understanding of the capsid structure of the virus.


Timing and cue competition in conditioning of the nictitating membrane response of the rabbit (Oryctolagus cuniculus).
Rabbits were classically conditioned using compounds of tone and light conditioned stimuli (CSs) presented with either simultaneous onsets (Experiment 1) or serial onsets (Experiment 2) in a delay conditioning paradigm. Training with the simultaneous compound reduced the likelihood of a conditioned response (CR) to the individual CSs ("mutual overshadowing") but left CR timing unaltered. CR peaks were consistently clustered around the time of unconditioned stimulus (US) delivery. Training with the serial compound (CSA→CSB→US) reduced responding to CSB ("temporal primacy/information effect") but this effect was prevented by prior CSB→US pairings. In both cases, serial compound training altered CR timing. On CSA→CSB test trials, the CRs were accelerated; the CR peaks occurred after CSB onset but well before the time of US delivery. Conversely, CRs on CSB- trials were decelerated; the distribution of CR peaks was variable but centered well after the US. Timing on CSB- trials was at most only slightly accelerated. The results are discussed with respect to processes of generalization and spectral timing applicable to the cerebellar and forebrain pathways in eyeblink preparations.


Ileal rhabdomyosarcoma in a patient with a history of squamous cell lung cancer.
Rhabdomyosarcoma is an infrequent muscular cancer seen in adults. We present a case of ileal intussusception due to pleomorphic rhabdomyosarcoma in a patient diagnosed previously with squamous cell carcinoma of the lung (SCCL). The patient was a 68-year-old man with a history of SCCL. He was admitted to the emergency department for nausea, emesis and obstipation. Surgical investigation of the abdomen revealed an intussusception caused by a tumour located 160cm distal of the ligament of Treitz. Pathological examination showed that tumour was a primary rhabdomyosarcoma of the ileum. This case contributes to the literature by defining an infrequent presentation of rhabdomyosarcoma causing ileal intussusception in an adult patient.


Ethical Dilemmas for Oocyte Donations: Slippery Slope for Conflicts of Interest.
Oocyte donations have increased with improvements in oocyte cryopreservation procedures in recent years. Women with medical conditions that require chemotherapy or radiotherapy have begun to opt for oocyte cryo¬preservation prior to their treatment or to enroll in an oocyte donation program. Alternatively, some women apply for "third-party" oocyte donation programs for nonmedical reasons such as delayed childbearing. Although society seems to accept oocyte donations for medical reasons, it appears that there are still some moral issues surrounding nonmedical oocyte donations. In this review, the ethical aspects of oocyte donations and donors' perspectives are discussed. With developing technologies, the genetic screening of donors has expanded to include diseases. This review explores the ethical issues involved in genetic screening of gamete donors.


Rapid Trio Exome Sequencing for Autosomal Recessive Renal Tubular Dysgenesis in Recurrent Oligohydramnios.
Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the AGT gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G > T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. AGT gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally.


Treatment of complicated pulmonary echinococcosis with albendazole in childhood.
The case of an 11-year-old boy suffering from pulmonary hydatid disease with rupture and bacterial superinfection is presented. After 3 courses of chemotherapy with albendazole the boy recovered fully, uneventfully and without relapse. Conservative management should always be considered before surgical intervention in children with echinococcosis, even when complications have occurred.


Psychological stress impairs short-term muscular recovery from resistance exercise.
The primary aim of this study was to determine whether chronic mental stress moderates recovery of muscular function, perceived energy, fatigue, and soreness in the first hour after a bout of strenuous resistance exercise. Thirty-one undergraduate resistance training students (age = 20.26 ± 1.34 yr) completed the Perceived Stress Scale and Undergraduate Stress Questionnaire (USQ; a measure of life event stress) and completed fitness testing. After 5 to 14 d of recovery, they performed an acute heavy-resistance exercise protocol (10-repetition maximum (RM) leg press test plus six sets: 80%-100% of 10 RM). Maximal isometric force (MIF) was assessed before exercise, after exercise, and at 20, 40, and 60 min postexercise. Participants also reported their levels of perceived energy, fatigue, and soreness. Recovery data were analyzed with hierarchical linear modeling growth curve analysis. Life event stress significantly moderated linear (P = 0.013) and squared (P = 0.05) recovery of MIF. This relationship held even when the model was adjusted for fitness, workload, and training experience. Likewise, perceived stress moderated linear recovery of MIF (P = 0.023). Neither USQ nor Perceived Stress Scale significantly moderated changes in energy, fatigue, or soreness. Life event stress and perceived stress both moderated the recovery of muscular function, but not psychological responses, in the first hour after strenuous resistance exercise.


Periodic lateralized epileptiform discharges: etiology, clinical aspects, seizures, and evolution in 130 patients.
The purpose of this study was to analyze the clinical aspects in 130 patients presenting periodic lateralized epileptiform discharges (PLEDs) in their EEG and to compare these results with those found in the literature. Etiology, neurologic deficit, seizure occurrence, and evolution were studied in each patient by historical review. The recordings were obtained on 8- or 16-channel EEGs with electrode placement according to the International 10-20 System. Recordings containing PLEDs were selected. PLEDs were defined as repetitive periodic, focal, or hemispheric epileptiform discharges (spikes, spike and waves, polyspikes, sharp waves) usually recurring every 1 to 2 seconds. The statistical study was carried out via the chi(2) test using the computer program SPSS. The main etiology found in this group of patients was stroke (61 of 130 patients). Other processes found were brain infections, tumors, hematomas, and several other entities grouped together as miscellaneous (anoxic encephalopathy, subarachnoid hemorrhage, craniocerebral trauma, Creutzfeldt-Jacob disease, migraine, multiple sclerosis, and aminophylline intoxication). Half of these patients (65 of 130) developed seizures, mostly partial motor seizures. No significant relation between etiology and seizures was found (chi(2) = 2.81, P = 0.4222). Seizures recurred in 14 of 130 patients during a follow-up of 14.5 months. PLEDs were not recorded in any EEG at the time of seizure recurrence. PLEDs constitute a distinctive but uncommon EEG phenomenon of repetitive, periodic, and stereotyped lateralized complexes. In agreement with the literature, PLEDs were associated with an acute process and occurred early during the course of the illness in all patients studied and were usually associated with structural lesions, with stroke being the main etiology. Traditionally, seizures occur with PLEDs but it is also accepted that they can exist in patients who never develop epileptic activity, either clinically or electrically, as demonstrated in 50% of the patients studied. No significant association between seizures and any etiology could be found. It was not demonstrated that the occurrence of seizures may influence the outcome in any way.


Evaluation of axial length/total corneal refractive power ratio as a potential marker for ocular diagnosis of Marfan's syndrome in children.
To investigate whether the axial length (AL)/total corneal refractive power (TCRP) ratio is a sensitive and simple factor that can be used for the early diagnosis of Marfan's syndrome (MFS) in children. The relationship between the AL/TCRP ratio and the diagnosis of MFS for 192 eyes in 97 children were evaluate. The biological characteristics, including age, sex, AL, and TCRP, were collected from medical records. Receiver operating characteristic (ROC) curve analysis was performed to investigate whether the AL/TCRP ratio effectively distinguishes MFS from other subjects. The Youden index was used to re-divide the whole population into two groups according to an AL/TCRP ratio of 0.59. Of 96 subjects (mean age 7.46±3.28y) evaluated, 56 (110 eyes) had a definite diagnosis of MFS in childhood based on the revised Ghent criteria, 41 (82 eyes) with diagnosis of congenital ectopia lentis (EL) were included as a control group. AL was negatively correlated with TCRP, with a linear regression coefficient of -0.36 (R 2=0.08). A significant correlation was found between age and the AL/TCRP ratio (P=0.023). ROC curve analysis showed that the AL/TCRP ratio distinguished MFS from the other patients at a threshold of 0.59. MFS patients were present in 24/58 (41.38%) patients with an AL/TCRP ratio of ≤0.59 and in 34/39 (87.18%) patients with an AL/TCRP ratio of >0.59. An AL/TCRP ratio of >0.59 is significantly associated with the risk of MFS. The AL/TCRP ratio should be measured as a promising marker for the prognosis of children MFS. Changes in the AL/TCRP ratio should be monitored over time.


Regenerative medicine strategies for chronic complete spinal cord injury.
Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases. While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable, most research in this field has focused on the early phase of incomplete injury. However, the majority of patients have chronic severe injuries; therefore, treatments for these situations are of fundamental importance. The reason why the treatment of complete spinal cord injury has not been studied is that, unlike in the early stage of incomplete spinal cord injury, there are various inhibitors of neural regeneration. Thus, we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies. First, we established a combination therapy of cell transplantation and drug-releasing scaffolds, which contributes to functional recovery after chronic complete transection spinal cord injury, but we found that functional recovery was limited and still needs further investigation. Here, for the further development of the treatment of chronic complete spinal cord injury, we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss, with reference to the literature, which combination of treatments is most effective in achieving functional recovery.


Fc receptor-directed phagocytic stimuli induce transient actin assembly at an early stage of phagocytosis in neutrophil leukocytes.
The phagocytic pathway for the uptake of multivalent Fc complexes by neutrophil leukocytes can be partially dissected by using a pulse-chase protocol at different chase temperatures. Utilising a deoxyribonuclease I inhibition assay, we show that an early response to recognition of phagocytic substrate by neutrophils is a rapid (less than 10 sec) polymerization of actin. Net actin assembly is transient and is reversed at higher chase temperatures which appears to allow for further progress of the pulse of phagocytic substrate along the pathway. Assembly of actin monitored in whole cells is paralleled by an increase in total actin retained in the cortical filamentous network of detergent-insoluble ghosts prepared from phagocytosing neutrophils. These data provide direct evidence for the reversible reorganisation of actin filaments in the cortical cytoplasm of phagocytic cells during phagocytosis. Furthermore, this experimental system provides an opportunity to study the characteristics of ligand-induced actin assembly, and subsequent disassembly in situ.


A novel application of an adaptable modeling approach to the management of toxic microalgal bloom events in coastal areas.
Harmful algal blooms have been increasing in frequency in recent years, and attention has shifted from describing to modeling and trying to predict these phenomena, since in many cases they pose a risk to human health and coastal activities. Predicting ecological phenomena is often time and resource consuming, since a large number of field collected data are required. We propose a novel approach that involves the use of modeled meteorological data as input features to predict the concentration of the toxic benthic dinoflagellate Ostreopsis cf. ovata in seawater. Ten meteorological features were used to train a Quantile Random Forests model, which was then validated using field collected concentration data over the course of a summer sampling season. The proposed model was able to accurately describe Ostreopsis abundance in the water column in response to meteorological variables. Furthermore, the predictive power of this model appears good, as indicated by the validation results, especially when the quantile for predictions is tuned to match management requirements. The Quantile Random Forests method was selected, as it allows for greater flexibility in the generated predictions, thus making this model suitable as a tool for coastal management. The application of this approach is novel, as no other models or tools that are adaptable to this degree are currently available. The model presented here was developed for a single species over a limited geographical extension, but its methodological basis appears flexible enough to be applied to the prediction of HABs in general and it could also be extended to the case of other ecological phenomena that are strongly dependent on meteorological drivers, that can be independently modeled and potentially globally available.


Effect of optogenetic manipulation of accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine-induced behavioral sensitization.
Repetitive exposure to addictive drugs causes synaptic modification in the mesocorticolimbic dopamine (DA) system. Dopamine D1 receptors (D1R) or D2 receptors (D2R) expressed in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) play critical roles in the control of addictive behaviors. Optogenetic activation of D2R-expressing MSNs (D2R-MSNs) in the NAc previously demonstrated that these neurons play a key role in withdrawal-induced plasticity. Here, we examined the effect of optogenetic inhibition of D2R-MSNs in the NAc on cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding archaerhodopsin (ArchT) were delivered into the NAc of D2-Cre transgenic mice. Activation of ArchT produced photoinhibition of D2R-MSNs and caused disinhibition of neighboring MSNs in the NAc. However, such optogenetic silencing of D2R-MSNs in the NAc in vivo affected neither the initiation nor the expression of cocaine-induced behavioral sensitization. Similarly, photoinhibition of NAc D2R-MSNs in the NAc during the drug withdrawal period did not affect the expression of cocaine-induced behavioral sensitization. More detailed analysis of the effects of optogenetic activation of D2R-MSNs suggests that D2R-MSNs in the NAc exert important modulatory effects on neighboring MSN neurons, which may control the balanced output of NAc MSNs to control addictive behaviors.


Control of cotton fibre elongation by a homeodomain transcription factor GhHOX3.
Cotton fibres are unusually long, single-celled epidermal seed trichomes and a model for plant cell growth, but little is known about the regulation of fibre cell elongation. Here we report that a homeodomain-leucine zipper (HD-ZIP) transcription factor, GhHOX3, controls cotton fibre elongation. GhHOX3 genes are localized to the 12th homoeologous chromosome set of allotetraploid cotton cultivars, associated with quantitative trait loci (QTLs) for fibre length. Silencing of GhHOX3 greatly reduces (>80%) fibre length, whereas its overexpression leads to longer fibre. Combined transcriptomic and biochemical analyses identify target genes of GhHOX3 that also contain the L1-box cis-element, including two cell wall loosening protein genes GhRDL1 and GhEXPA1. GhHOX3 interacts with GhHD1, another homeodomain protein, resulting in enhanced transcriptional activity, and with cotton DELLA, GhSLR1, repressor of the growth hormone gibberellin (GA). GhSLR1 interferes with the GhHOX3-GhHD1 interaction and represses target gene transcription. Our results uncover a novel mechanism whereby a homeodomain protein transduces GA signal to promote fibre cell elongation.


Hesperidin: A Potential Therapeutic Agent against COVID-19.
COVID-19, aka Coronavirus Disease 2019, triggered by new severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2, is now a public health emergency due to its rapid spread, high transmission efficiency, and severe viral pandemic that is significantly increasing the number of patients and associated deaths. Currently, no specific treatment is available for this highly contagious virus. The unavailability of effective and specific treatments and the severity of this epidemic situation potentiate medicinal chemists' in supporting new prophylactic or therapeutic interventions against COVID-19. This study discusses the therapeutic potential of hesperidin, a traditionally used herbal medicine with an exceptional safety profile. Recent studies on hesperidin advocate its promising potential in the prevention and management of COVID-19. This paper also discusses the recent clinical studies based on the previously documented antiviral activity of hesperidin. Herein, we propose the detailed preclinical and clinical manifestations of hesperidin based on its multifaceted bioactivities to develop a novel anti-COVID-19 lead.


Prevalence of intestinal parasites in street dogs (Canis lupus familiaris) with highlights on zoonosis in Lalitpur, Nepal.
The presence of intestinal parasites influences the growth and well-being of canids. Additionally, infected dogs and their faeces with considerably higher eggs/oocysts released per gram (epg/opg) of zoonotic parasites contribute to parasitic spillover to humans, domestic animals and sympatric wildlife. The current study aimed to reveal the prevalence of intestinal parasites (protozoa and helminths) and to list the zoonotically significant parasites in free-roaming street dogs in Lalitpur Metropolitan City, Nepal. Fresh faecal samples (n = 332) were collected from feral dogs of varying ages and sexes and transported to the research laboratory. The copro microscopic examination was carried out via direct wet mount, formalin ethyl acetate sedimentation, saturated salt flotation, acid-fast staining and sporulation techniques. Coproscopy revealed an overall 95.7% (318/332) prevalence rate with 23 diverse species of intestinal parasites (10 protozoa and 13 helminths). Among them, 5 protozoa and 11 helminths possessed zoonotic potential, and their overall prevalence was 92.5%. Helminth's overall prevalence was double that of the protozoa (87.7% vs. 43%). Polyparasitism was dominant over mono parasitism (79.5% vs. 16.3%), and co-infection of up to seven species of parasites at a time was recorded. Urban street dogs harboured a higher prevalence of intestinal parasites that varied with age and sex. Since most of the reported parasites are zoonotic, dog density and parasitic richness indicate a greater spillover risk to humans and domestic animals. Furthermore, this study also provides appropriate 'baseline' data for assessing effective control measures against parasitic infestations among street dogs and controlling their transmission to humans.


[Incidence of sudden cardiac death in relation to left ventricular anatomy and rhythm profile (author's transl)].
204 patients, undergoing coronary and left ventricular (LV) angiography as well as long-term ECG monitoring (20 and 24 hours, Meditape K, Siemens; Pathfinder, Reynolds), were followed for an average of 18.2 months (1-50 months); all showed obstructions of greater than or equal to 75% of one or several coronary branches (LAD, LCX, RCA); qualitative and quantitative assessment of poststenotic LV wall motion (PWM) (percent shortening of 18 halfaxes) revealed akinesis or dyskinesis (A/D) in 55%, hypokinesis in 29 and normokinesis in 16% of the cases. Long-term ECG-monitoring showed a sign. (p less than 0.025) correlation between PWM, esp. A and D and ventricular extrasystoles (VES) of Lown-Classes IV/V and N i.e. Lown-Classes 0-II, as well as the extent of the akinetic region. However, correlation between the extent of coronary disease (number of abnormal vessels) and VES was weak. -- 19 patients died suddenly i.e. within one hour (mortality 9.3%, i.e. 6.1% per year); 10 patients were in Lown-Class IV/V (53%), 15 (79%) showed A or D, 4 (21%) H in the LV angiogram; in no case was PWM normal. Correlation between degree of VES (Lown-Classes) and mortality was not sign. (mortality for Lown-Classes 0-II = 5.4%, III = 7.9%, IV/V = 14.9%); however, mortality correlated sign. (p less than 0.025) with PWM (for D/A = 16.3%, H = 4.4%, N = 0%). The highest mortality (10/39 cases) of 25.6% i.e. 16.8% per year was found in patients with Lown-Classes IV/V and dys- or akinetic PWM. Thus, in patients with chronic CHD, severity of VES cannot be considered as an independent prognostic factor, but only in connection with the abnormal LV anatomy.


Dynamic plasma EGFR mutation status as a predictor of EGFR-TKI efficacy in patients with EGFR-mutant lung adenocarcinoma.
Epidermal growth factor receptor (EGFR) mutation status in lung cancer can effectively predict EGFR-tyrosine kinase inhibitor (TKI) efficacy. We evaluated the role of dynamic plasma cell-free DNA EGFR mutation status in outcome prediction. Advanced lung adenocarcinoma patients were enrolled and prospectively observed for outcomes of EGFR-TKI treatment. Peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method was developed to assess EGFR mutations in matched tumor and serial plasma cell-free DNA specimens. A total of 72 patients were enrolled in this study, of which 62 patients (86.1%) had EGFR-mutant tumors (34 patients with exon 19 deletions, and 28 patients with L858R). Pretreatment plasma used for EGFR mutation testing showed a sensitivity of 59.7% and a specificity of 100%. Detection sensitivity was significantly higher in stage IV-M1b patients compared with stage IIIb and IV-M1a patients (78.0% versus 23.8%, p < 0.001). All patients who presented with EGFR-mutant tumors received first-line EGFR-TKI therapy. The objective response rate and disease control rate were 74.2% and 82.3%, respectively. Median progression-free survival and overall survival were 8.8 months (95% CI: 6.6-11.0) and 20.5 months (95% CI 15.1-26.0), respectively. Failure to clear plasma EGFR mutations after EGFR-TKI treatment was an independent predictor of lower disease control rate (odds ratio 5.26 [95% CI: 1.13-24.44]; p = 0.034), shorter progression-free survival (hazard ratio: 1.97 [95% CI: 1.33-2.91]; p = 0.001), and shorter overall survival (hazard ratio: 1.82 [95% CI: 1.04-3.18], p = 0.036). Changes in plasma EGFR mutation status can be successfully assessed using the peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method and can serve as an independent outcome predictor.


In vitro antispasmodic compounds of the dry extract obtained from Hedera helix.
Commercial dry extract of Hedera helix L. is used for the treatment of disorders of the respiratory tract; it is standardized towards papaverine (papaverine equivalent value, PE, activity of 1 g test substance equivalent to the activity of x mg papaverine) by in vitro antispasmodic activity on isolated guinea-pig ileum with acetylcholine as spasmogen. In order to determine the phytochemical basis for the antispasmodic activity, bioassay guided fractionation and subsequent isolation of phenolic compounds (flavonols, caffeoylquinic acids) and saponins (hederacoside C, alpha-hederin, hederagenin) was carried out. Fractions and isolates obtained were investigated for antispasmodic activity and their contribution to the activity of the extract was calculated. Significant activity was found for both saponins and phenolic compounds, the PE values being approx. 55 and 49 for alpha-hederin and hederagenin, 54 and 143 for quercetin and kaempferol, and 22 for 3,5-dicaffeoylquinic acid, respectively. In view of their relative high concentration the saponins contribute most to the anti-spasmodic activity, followed by dicaffeoylquinic acids and the flavonol derivatives. The results indicate that the summed PE value of the compounds mentioned is an acceptable agreement with the PE value of the whole extract determined biologically.


Finding vulnerable subpopulations in the Seychelles Child Development Study: effect modification with latent groups.
The Seychelles Child Development Study is a research project with the objective of examining associations between prenatal exposure to low doses of methylmercury from maternal fish consumption and children's developmental outcomes. Whether methylmercury has neurotoxic effects at low doses remains unclear and recommendations for pregnant women and children to reduce fish intake may prevent a substantial number of people from receiving sufficient nutrients that are abundant in fish. The primary findings of the Seychelles Child Development Study are inconsistent with adverse associations between methylmercury from fish consumption and neurodevelopmental outcomes. However, whether there are subpopulations of children who are particularly sensitive to this diet is an open question. Secondary analysis from this study found significant interactions between prenatal methylmercury levels and both caregiver IQ and income on 19-month IQ. These results are sensitive to the categories chosen for these covariates and are difficult to interpret collectively. In this paper, we estimate effect modification of the association between prenatal methylmercury exposure and 19-month IQ using a general formulation of mixture regression. Our mixture regression model creates a latent categorical group membership variable which interacts with methylmercury in predicting the outcome. We also fit the same outcome model when in addition the latent variable is assumed to be a parametric function of three distinct socioeconomic measures. Bayesian methods allow group membership and the regression coefficients to be estimated simultaneously and our approach yields a principled choice of the number of distinct subpopulations. The results show three groups with different response patterns between prenatal methylmercury exposure and 19-month IQ in this population.


Diagnosis of ganglionar tuberculosis by endoscopic ultrasonography.
The endoscopic ultrasonography (EUS) is an endoscopic technique of proven clinical validity today, having a significant impact on the diagnosis and evaluation of several diseases with a low complication rate. The EUS-fine-needle aspiration (FNA) allows the evaluation of subepithelial lesions, extra-luminal lymph nodes or the gastrointestinal tract that are difficult to access by other methods with safe and high diagnostic accuracy. In the case reported, the EUS-FNA was useful for the differential diagnosis with residual biliary microlithiasis and the diagnosis of non-oncologic pathology. Male, white, 35-year-old, human immunodeficiency virus and tuberculosis treatment for about 5 months presented with jaundice. No fever, weight loss or abdominal pain. Choluria and hipocholia. History of cholecystectomy for about 1 year due to cholelithiasis. Laboratory tests showed cholestatic jaundice (direct hyperbilirrubinemia). Abdominal ultrasound showed liver without particularities, without biliary dilatation or filling defects. Initially suspected hepatitis due tuberculosis drugs so, the treatment was suspended. After a week with no drugs, no improvement in jaundice was observed. In contrast, a progressive increase indirect bilirubin. EUS performed with identification of mass along the distal common bile duct near the duodenal papilla. FNA performed with the presence of lymphocytes and tuberculosis bacile positive. After, endoscopic retrograde cholangiopancreatography was performed with sphincterotomy and placement of endoprosthesis for biliary drainage. The tuberculosis drugs were restarted with the plan to complete. The jaundice was resoluted. The patient completed 9 months of treatment and abdominal tomography has not identified a mass in that place. The EUS-FNA was proven to be a useful tool for diagnosis of non-oncologic pathologies like tuberculosis.


A synthetic method suitable for the rapid preparation of 13N-labeled dermorphin analogue, H-Tyr-D-Met(O)-Phe-Gly-NH2 (SD-62).
A synthetic method suitable for the preparation of 13N-labeled dermorphin analogue, H-Tyr-D-Met(O)-Phe-Gly-NH2 (SD-62), was established; i.e., SD-62 was synthesized by a 5 min treatment of the active ester precursor with ammonia. When the 13N-labeled SD-62, prepared by this method with [13N]ammonia, was administered into mice, the time profile of the radioactivity accumulation in the brain paralleled well that of the analgesic activity.


[The level of asthma control in China from a national asthma control survey].
Objective: To assess the overall asthma control level in urban China. Methods: A multi-center, cross-sectional, questionnaire-based survey was carried out in 30 provinces in China (except Tibet). Asthmatic outpatients who met the inclusion criteria were recruited consecutively from 30 sub-centers from October 2015 to May 2016. Data of demographic characteristics, asthma control, asthma management, asthma exacerbations and self-management, and disease perception were collected by face-to-face interviews. Results: Totally 3 875 asthmatic outpatients were recruited. Asthma control level was assessed according to GINA 2015. The prevalence of asthma control was 28.5%(1 099/3 854). Among 10 cities, which were also involved in the asthma control survey in 2008, the level of asthma control improved from 28.7% in 2008 to 39.2%(533/1 361) in 2016. The rate of hospitalizations due to asthma exacerbations was 26.4%(1 017/3 858) and the rate of emergency visits was 22.4%(864/3 858). Among adult patients, 18.4%(568/3 092) of them had been absent from work while 63.6%(63/99) adolescent patients had been absent from school because of asthma attacks in the previous year. Conclusion: Although the level of asthma control in China is still far from ideal at present, the status has been improved in some cities. Poorly controlled asthma resulted in increase of hospitalizations, emergency department visits and work/school absences.


Stereotype threat effects on Italian girls' mathematics performance: A failure to replicate.
Many studies have found that males, on average, perform better than females in mathematics, although the size of this gender gap is small and varies considerably across countries. Stereotype threat has been proposed as a principal cause of this gender gap. From this perspective, females' performance is affected by fear of confirming a negative stereotype about females' mathematical ability and this stereotype can be activated by an experimental manipulation that reminds females of the stereotype. Yet, evidence of a stereotype threat effect on mathematics performance in childhood and adolescence has been mixed. The present study replicated a highly cited study of stereotype threat among Italian adolescents with a much larger sample of Italian ninth grade (89 male, 75 female, mean age = 14.2) and eleventh grade (84 male, 80 female, mean age = 16.2) public high school students. Performance in tests administered both before and after the experimental manipulations were analyzed with a series of logistic mixed-effects models. Model comparisons confirmed that males performed better than females, but the probability of a stereotype threat effect was infinitesimal. We conclude that Italian adolescent gender differences in mathematics may not be explained by stereotype threat effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Hormonal counterregulatory responses to human (semi-synthetic and recombinant DNA) and porcine insulin induced hypoglycaemia.
Controversy exists over differences in hormonal counterregulatory (CR) responses to human and porcine insulins with conflicting reports regarding the adrenaline, glucagon, growth hormone, cortisol and prolactin responses to the two species of insulin. It has been suggested that these differences may represent different central nervous system sensitivities to the two types of insulin. The CR responses to an intravenous bolus of 0.1 U/kg of neutral soluble semi-synthetic (SSHI) and biosynthetic (BHI) human insulins, porcine insulin and diluting medium as control were compared in six fasted normal male subjects. The plasma glucose fell similarly with all three insulins reaching a mean nadir of 1.5 +/- 0.2 mmol/l at 25 min. Peak responses to porcine, SSHI and BHI, respectively were: adrenaline--523 +/- 101, 424 +/- 62, 379 +/- 76 pg/ml; glucagon--0.064 +/- 0.01, 0.063 +/- 0.01, 0.078 +/- 0.01 nmol/l; cortisol--507 +/- 42, 539 +/- 65, 507 +/- 42 nmol; growth hormone--76 +/- 10, 76 +/- 5, 64 +/- 15 mU/l; prolactin--507 +/- 72, 608 +/- 103, 523 +/- 118 mU/l. These differences in CR response were not statistically significant. The results do not support the suggestion of a different hormonal counterregulatory response or central nervous system sensitivity to human and porcine insulins when administered by intravenous bolus injections to normal subjects.


Zirconium-based metallic glass and zirconia coatings to inhibit bone formation on titanium.
Surface-modified commercially pure titanium (Cp-Ti) with zirconium (Zr)-based thin film metallic glasses (Zr-TFMGs) and ZrO2 thin films were surgically implanted into the tibiae of rats; the bone formation was analyzed to examine the performance of the coatings as a biomaterial. Zr-TFMGs and ZrO2 thin films were coated on Cp-Ti substrates to monitor the control of assimilation in vitro and in vivo. The microstructural and elemental analyses were carried out for the as deposited thin films by x-ray diffraction (XRD), transmission electron microscopy and x-ray photoelectron spectroscopy. TFMG- and ZrO2-coated Ti specimens were immersed in simulated body fluid (SBF) for a period of 21 days to evaluate the calcium phosphate precipitation in vitro. XRD, x-ray photoelectron spectroscopy and scanning electron microscopy/energy dispersive x-ray spectroscopy were used to quantify the mineralization on the coated Zr-TFMG and ZrO2. In vitro corrosion studies showed that the Zr-based TFMG and ZrO2 coatings sustained in the SBF, exhibited superior corrosion resistance to the bare crystalline Ti substrate. Wettability studies showed TFMG and ZrO2 coatings with a hydrophobic nature, and the TFMG-coated SBF-submerged specimens showed a hydrophilic nature. The in vitro cell viability of MC3T3-E1 cells showed good cell proliferation and low cytotoxicity. The calcification deposits were evaluated by staining with alizarin red S, which showed a lower calcium formation on Zr-TFMG compared to ZrO2. The present work also aims to assess the assimilation behavior of Cp-Ti, Zr-TFMG and ZrO2 in vivo by inserting the coated specimen in the femur of rats. After post-implantation of 8 weeks, specimens were examined by micro-CT evaluation. The bone contact ratios as calculated were 72.75%, 15.32% and 38.79%. Consequently, the bone affinity was Cp-Ti wire >ZrO2-coated Ti wire >Zr48Cu36Ag8Al8-coated Ti wire.


Scalable Device for Automated Microbial Electroporation in a Digital Microfluidic Platform.
Electrowetting-on-dielectric (EWD) digital microfluidic laboratory-on-a-chip platforms demonstrate excellent performance in automating labor-intensive protocols. When coupled with an on-chip electroporation capability, these systems hold promise for streamlining cumbersome processes such as multiplex automated genome engineering (MAGE). We integrated a single Ti:Au electroporation electrode into an otherwise standard parallel-plate EWD geometry to enable high-efficiency transformation of Escherichia coli with reporter plasmid DNA in a 200 nL droplet. Test devices exhibited robust operation with more than 10 transformation experiments performed per device without cross-contamination or failure. Despite intrinsic electric-field nonuniformity present in the EP/EWD device, the peak on-chip transformation efficiency was measured to be 8.6 ± 1.0 × 108 cfu·μg-1 for an average applied electric field strength of 2.25 ± 0.50 kV·mm-1. Cell survival and transformation fractions at this electroporation pulse strength were found to be 1.5 ± 0.3 and 2.3 ± 0.1%, respectively. Our work expands the EWD toolkit to include on-chip microbial electroporation and opens the possibility of scaling advanced genome engineering methods, like MAGE, into the submicroliter regime.


A cross-cultural study of the reliability and factorial dimensions of the Nurses' Observation Scale for Inpatient Evaluation (NOSIE).
Investigated the reliability and factor structure of the Nurses' Observation Scale for Inpatient Evaluation (NOSIE) in a group of short-stay psychiatric patients (N = 247) of a Dutch psychiatric university clinic. It was found that the NOSIE has good interrater reliability. With the exception of the Social Competence and Personal Neatness subscales five of the original seven scales could be replicated when compared with American and British studies.


Role of glial 14-3-3 gamma protein in autoimmune demyelination.
The family of 14-3-3 proteins plays an important role in the regulation of cell survival and death. Here, we investigate the role of the 14-3-3 gamma (14-3-3 γ) subunit for glial responses in autoimmune demyelination. Expression of 14-3-3 γ in glial cell culture was investigated by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. 14-3-3 γ knockout mice were subjected to murine myelin oligodendrocyte-induced experimental autoimmune encephalomyelitis (MOG-EAE), an animal model mimicking inflammatory features and neurodegenerative aspects of multiple sclerosis (MS). Expression studies in cell culture confined expression of 14-3-3 γ to both, oligodendrocytes (OL) and astrocytes. RT-PCR analysis revealed an increased expression of 14-3-3 γ mRNA in the spinal cord during the late chronic phase of MOG-EAE. At that stage, EAE was more severe in 14-3-3 γ knockout mice as compared to age- and gender-matched controls. Histopathological analyses on day 56 post immunization (p.i.) revealed significantly enhanced myelin damage as well as OL injury and secondary, an increase in axonal injury and gliosis in 14-3-3 γ -/- mice. At the same time, deficiency in 14-3-3 γ protein did not influence the immune response. Further histological studies revealed an increased susceptibility towards apoptosis in 14-3-3 γ-deficient OL in the inflamed spinal cord. These data argue for a pivotal role of 14-3-3 γ-mediated signalling pathways for OL protection in neuroinflammation.


Occupational Noise-Induced Hearing Loss.
: Occupational hearing loss is preventable through a hierarchy of controls, which prioritize the use of engineering controls over administrative controls and personal protective equipment. The occupational and environmental medicine (OEM) physician plays a critical role in the prevention of occupational noise-induced hearing loss (NIHL). This position statement clarifies current best practices in the diagnosis of occupational NIHL.


Jamaican vomiting sickness. Biochemical investigation of two cases.
We identified methylenecyclopropylacetic acid, a known metabolite of hypoglycin A, in the urine of two patients with Jamaican vomiting sickness. Excretion of unusual dicarboxylic acids such as 2-ethylmalonic, 2-methylsuccinic, glutaric, adipic and dicarboxylic acids with eight and 10 carbon chains were also detected in both patients. The amounts of these dicarboxylic acids were 70 to 1000 times higher than normal. These metabolites have also been identified in urine of hypoglycin-treated rats. This evidence links hypoglycin A to Jamaican vomiting sickness as its causative agent. Urinary excretion of short-chain fatty acids was also increased up to 300 times higher than normal. These results indicate that, despite their clinical and histologic similarities, the cause and biochemical mechanisms of Jamaican vomiting sickness differ distinctly from those of Reye's syndrome in which these abnormal urinary metabolites are not appreciably increased.


Prone decubitus: a solution to inferior wall attenuation in thallium-201 myocardial tomography.
We propose an efficient method to suppress inferior wall attenuation in 201TI 180 degrees myocardial tomography. We systematically performed redistribution studies in both supine and prone decubitus, assuming that the latter should result in shifting with respect to each other's cardiac structures and diaphragm as well as subphrenic organs possibly responsible for attenuation. The comparison of both studies in 25 normal subjects by visual interpretation and circumferential profiles analysis showed a complete suppression of significant attenuation in the inferior wall in prone studies. In addition and consequently, the standard deviation of activity in this area was markedly reduced and became close to its value in anterior and lateral walls. This simple technique now routinely performed in over 400 patients drastically improves specificity in the evaluation of inferior wall abnormalities by suppressing attenuation artifacts and, incidently, the effect of high individual variability in left phrenic and subphrenic anatomic configuration.


Prevalent fingerprint of marine macroalgae in arctic surface sediments.
Macroalgal forests export much of their production, partly supporting food webs and carbon stocks beyond their habitat, but evidence of their contribution in sediment carbon stocks is poor. We test the hypothesis that macroalgae contribute to carbon stocks in arctic marine sediments. We used environmental DNA (eDNA) fingerprinting on a large-scale set of surface sediment samples from Greenland and Svalbard. We evaluated eDNA results by comparing with traditional survey and tracer methods. The eDNA-based survey identified macroalgae in 94 % of the sediment samples covering shallow nearshore areas to 1460 m depth and 350 km offshore, with highest sequence abundance nearshore and with dominance of brown macroalgae. Overall, the eDNA results reflected the potential source communities of macroalgae and eelgrass assessed by traditional surveys, with the most abundant orders being common among different methods. A stable isotope analysis showed a considerable contribution from macroalgae in sediments although with high uncertainty, highlighting eDNA as a great improvement and supplement for documenting macroalgae as a contributor to sediment carbon stocks. Conclusively, we provide evidence for a prevalent contribution of macroalgal forests in arctic surface sediments, nearshore as well as offshore, identifying brown algae as main contributors.


Functional differentiation of virgin mouse mammary epithelium in explant culture is dependent upon extracellular proline.
Depletion of proline from insulin, hydrocortisone, and prolactin-containing medium prior to incubating virgin mouse mammary explants prevents both DNA synthesis and functional differentiation in the mammary epithelial cells; however, DNA synthesis in the mammary stroma and total incorporation of radioactive amino acids into total protein appears to continue without hindrance. Removal of glycine instead of proline had no deleterious effect on either DNA replication in the hormone-stimulated epithelium or in its functional differentiation. Functional differentiation was determined by the induction of casein and alpha-lactalbumin synthesis in the insulin, hydrocortisone, and prolactin (IFPrl)-treated explant cultures. As a control, the induction of mouse mammary tumor virus (MMTV) gene expression, a corticosteroid-regulated function, was also measured. Neither the absence of proline or glycine prevented the glucocorticoid stimulation of MMTV gene expression. In contrast to mammary tissue from virgin mice, explants from nonpregnant primiparous mice responded fully to IFPrl stimulation with respect to DNA, casein, and alpha-lactalbumin synthesis in medium depleted of proline. These data suggest that the uncommitted epithelium of virgin mouse mammary glands requires the presence of exogenous proline in order to respond to lactogenic hormonal signals. We have demonstrated earlier that DNA synthesis is a prerequisite of functional differentiation in virgin mouse mammary explants (Smith and Vonderhaar, 1981, Dev. Biol., 88:167-179; Vonderhaar and Smith, 1982, J. Cell Sci, 53:97-114), although cytological differentiation proceeded unencumbered in explants prevented from synthesizing DNA. Here, without proline, neither cytological nor functional differentiation can be induced; this suggests that proline provides an essential metabolic interlock in the acquisition of lactogenic hormone responsiveness in uncommitted mouse mammary tissue.


Professionalism in Physician Assistant Education as a Predictor of Future Licensing Board Disciplinary Actions.
The purpose of this study was to evaluate associations between postgraduate disciplinary actions (PGDA) by state licensing boards and physician assistant (PA) school documented professionalism violations (DPV) and academic probation. This was a retrospective cohort study comprising PA graduates from 2001 to 2011 at 3 institutions (n = 1364) who were evaluated for the main outcome of PGDA and independent variable of DPV and academic probation. Random-effects multiple logistic regression and accelerated failure time parametric survival analysis were used to investigate the association of PGDA with DPV and academic probation. Postgraduate disciplinary action was statistically significant and positively associated with DPV when unadjusted (odds ratio [OR] = 5.15; 95% CI: 1.62-16.31; P = .01) and when adjusting for age, sex, overall PA program GPA (GPA), and Physician Assistant National Certifying Exam Score (OR = 5.39; 95% CI: 1.54-18.85; P = .01) (fully adjusted). Academic probation increased odds to 8.43 times (95% CI: 2.85-24.92; P < .001) and 9.52 times (95% CI: 2.38-38.01; P < .001) when fully adjusted. Students with professionalism violation or academic probation while in the PA school had significant higher odds of receiving licensing board disciplinary action compared with those who did not. Academic probation had a greater magnitude of effect and could represent an intersection of professionalism and academic performance.


Orally active prostacyclin analogue for cardiovascular disease.
Prostacyclin has vasoprotective effects such as vasodilation and antiplatelet aggregatory activity. A relative deficiency of prostacyclin contributes to the pathogenesis of cardiovascular disease including pulmonary artery disease (PAH). Inconvenient intravenous dosing of prostacyclin led to the development of more stable, an orally active analogue: beraprost. It is a chemically stable prostacyclin analogue owing to its cyclo-pentabenzofuranyl structure and produces strong vasodilation and inhibition of platelet aggregation. To date, beraprost has been used in the treatment of PAH and peripheral arterial disease (PAD). Recently, we have shown that beraprost induces neovascularization in ischemic myocardium by enhancement of bone marrow cell mobilization. Interestingly, meta-analysis of clinical studies for PAD has shown that repeated administration of beraprost decreases the number of cardiovascular events. These results suggest that oral administration of beraprost has beneficial effects on cardiovascular disease. Orally active prostacyclin analogues, are promising drugs for the treatment of cardiovascular disease.


A potential neuroprotective role of apolipoprotein E-containing lipoproteins through low density lipoprotein receptor-related protein 1 in normal tension glaucoma.
Glaucoma is an optic neuropathy and the second major cause of blindness worldwide next to cataracts. The protection from retinal ganglion cell (RGC) loss, one of the main characteristics of glaucoma, would be a straightforward treatment for this disorder. However, the clinical application of neuroprotection has not, so far, been successful. Here, we report that apolipoprotein E-containing lipoproteins (E-LPs) protect primary cultured RGCs from Ca(2+)-dependent, and mitochondrion-mediated, apoptosis induced by glutamate. Binding of E-LPs to the low density lipoprotein receptor-related protein 1 recruited the N-methyl-d-aspartate receptor, blocked intracellular Ca(2+) elevation, and inactivated glycogen synthase kinase 3β, thereby inhibiting apoptosis. When compared with contralateral eyes treated with phosphate-buffered saline, intravitreal administration of E-LPs protected against RGC loss in glutamate aspartate transporter-deficient mice, a model of normal tension glaucoma that causes glaucomatous optic neuropathy without elevation of intraocular pressure. Although the presence of α2-macroglobulin, another ligand of the low density lipoprotein receptor-related protein 1, interfered with the neuroprotective effect of E-LPs against glutamate-induced neurotoxicity, the addition of E-LPs overcame the inhibitory effect of α2-macroglobulin. These findings may provide a potential therapeutic strategy for normal tension glaucoma by an LRP1-mediated pathway.


Plasma pooling methodology as a faster and cheaper tool to evaluate bioequivalence of rifampicin component of FDCs of antitubercular drugs.
Rifampicin is one of the most important first line drugs used in fixed dose combinations (FDCs) of antitubercular drugs. The chances of reduced bioavailability of rifampicin from FDCs necessitated its evaluation against standard formulations of individual drugs in bioequivalence studies. This study was undertaken to evaluate the importance of plasma pooling methodology as a rapid and cheaper tool to evaluate bioequivalence of rifampicin component of FDCs of antitubercular drugs. Plasma samples of volunteers obtained from bioequivalence studies were pooled according to volunteer and time-wise pooling. Area under the plasma concentration versus time curves (AUCs) of rifampicin was reduced in the pooled plasma samples when compared to the individual samples. However, the ratio of AUCs of FDCs to that of separate formulations was found to be comparable for both the individual samples and pooled samples data. Concentration-time profiles of rifampicin obtained after time-wise pooling were subjected to non-compartmental analysis for determination of pharmacokinetic parameters. Whereas bioequivalence estimates were determined using individual AUC values obtained from volunteer-wise pooling. Results indicated the possibility of using plasma pooling methodology in bioequivalence estimation of rifampicin to simplify and accelerate the registration process.


Effects of bioactive glass with high phosphorus content on mineralization of type I collagen fibrils.
To study effects of bioactive glass with high phosphorus content (10.8% P2O5, 54.2% SiO2, 35% CaO, mol%, named PSC) on mineralization of type I collagen fibrils. (1) PSC, and PSC combining 0.1 mg/mL, 0.5 mg/mL, or 1.0 mg/mL polyacrylic acid (PAA), were used to induce the mineralization of self-assembled type I collagen fibrils. After 3 and 7 days of mineralization, collagen fibrils were observed by transmission electron microscopy (TEM) and selected area electron diffraction (SAED). (2) PSC suspension was dialyzed in simulated body fluid (SBF), or in SBF containing 0.1 mg/mL, 0.5 mg/mL, or 1.0 mg/mL PAA, to form amorphous calcium phosphate (ACP), then observed by TEM. (1) PSC and PSC combining 0.1 mg/mL or 0.5 mg/mL PAA induced mainly extrafibrillar mineralization. PSC combining 1.0 mg/mL PAA induced both extrafibrillar and intrafibrillar mineralization. (2) The ACP induced by PSC or PSC combining 0.1 mg/mL PAA partly formed lattice structure after 24 h. The particle size of the ACP induced by PSC combining 0.5 mg/mL PAA was 100-150 nm, and that induced by PSC combining 1.0 mg/mL PAA was 30-50 nm. PSC induced mainly extrafibrillar mineralization, and PSC combining an appropriate concentration (1.0 mg/mL) of PAA induced both extrafibrillar and intrafibrillar mineralization.


Supramolecular Arene-Ruthenium Metallacycle with Thermotropic Liquid-Crystalline Properties.
Functionalization of 1,4-di(4-pyridinyl)benzene with poly(arylester) dendrimers bearing cyanobiphenyl end-groups gives a bidentate dendromesogenic ligand (L) that exhibits thermotropic liquid-crystalline properties. Combination of the diruthenium complex [Ru2(p-cymene)2(donq)][DDS]2 (M) with L, by coordination-driven self-assembly, affords the discrete and well-defined metallacycle M2L2. Like L, this supramolecular dendritic system displays mesomorphic properties above 50 °C. Both compounds L and M2L2 show smectic phases, characterized by a multilayered organization of the multiple components.


Prevalence of Fragile X Syndrome among children receiving special education and carrier states in first degree relatives.
Fragile X syndrome (FXS) is a genetically determined developmental disorder. Underlying genotype is cytosine-guanine-guanine (CGG) repeat expansions with over 200 repeats in the fragile X mental retardation 1 (FMR1) gene. Children with FXS are most accessible in special education institutions in Sri Lanka, with a total of approximately 6000 registered attendees. The aim of the current study was to estimate the prevalence of FXS among special school attendees and to screen first degree relatives of affected children. A nationally representative sample of 850 children (5-18 years) was selected using multi-level stratified sampling. Screening was performed by 3' direct triplet primed PCR, followed by melting curve analysis. Expanded repeat status of the screened positives were confirmed using capillary electrophoresis, methylation specific PCR and Southern hybridization. Screening of available first degree relatives (n=12) were carried out using the same method of screening and diagnosis. Eleven had FXS. Prevalence of FXS was 1.3% (95% CI 0.9-1.6). Among the 11 with FXS 9 had more than 350 CGG repeats, while the rest had around 300. Twelve first degree relatives consisting of nine mothers, two female siblings and a male sibling were tested. All mothers and female siblings had either full mutation or premutation while the male sibling had CGG repeats in the normal range. Among the special school attendees, prevalence of FXS was 1.3% which has a high risk for autism and attention deficit hyperactivity disorder.


Taurodontism and length of teeth in patients with oligodontia.
Taurodontism and a reduced tooth length are reported to occur in patients with oligondontia. The aim of this study was to evaluate the occurrence of these factors in Dutch patients with oligodontia. Panoramic radiographs of 117 patients with oligodontia and 91 controls were collected. Taurodontism of the mandibular first molars was recorded and the length of cuspids, bicuspids and first molars of the mandible were measured. In patients with oligodontia 28.9% showed taurodontism of one or two mandibular first molars. The prevalence of taurodontism in normal Dutch subjects was 9.9%. No significant differences were found between the two sexes in both groups. Neither was there a significant difference in the unilateral and bilateral occurrence of taurodontism. The present findings supported the hypothesis that taurodontism may be the result of an ectodermal defect and a manifestation of developmental instability in patients with oligodontia. The length of mandibular cuspids and first molars in females were significantly reduced. In males only the lower right first molar was significantly reduced. The reduced length of the teeth may also be the result of a defect in ectodermal cells. Both taurodontism and a reduced length are of importance considering dental therapy.


Developmental changes of optical properties in neonates determined by near-infrared time-resolved spectroscopy.
Near-infrared spectroscopy has been used for measurement of changes in cerebral Hb concentrations in infants to study cerebral oxygenation and hemodynamics. In this study, measurements by time-resolved spectroscopy (TRS) were performed in 22 neonates to estimate the values of light absorption coefficient and reduced scattering coefficient (mu'(s)), cerebral Hb oxygen saturation (SCO2), cerebral blood volume (CBV), and differential pathlength factor (DPF), and the relationships between postconceptional age and mu'(s), SCO2, CBV, and DPF were investigated. A portable three-wavelength TRS system with a probe attached to the head of the neonate was used. The mean mu'(s) values at 761, 795, and 835 nm in neonates were estimated to be (mean +/- SD) 6.46 +/- 1.21, 5.90 +/- 1.15 and 6.40 +/- 1.16/cm, respectively. There was a significant positive relationship between postconceptional age and mu'(s) at those three wavelengths. The mean SCO2 value was calculated to be 70.0 +/- 4.6%, and postconceptional age and SCO2 showed a negative linear relationship. The mean value of CBV was 2.31 +/- 0.56 mL/100 g. There was a significant positive relationship between postconceptional age and CBV. The mean DPF values at 761, 795, and 835 nm were estimated to be 4.58 +/- 0.41, 4.64 +/- 0.46, and 4.31 +/- 0.42, respectively. There was no relationship between postconceptional age and DPF at those three wavelengths. The results demonstrated that our near-infrared TRS method can be used to monitor mu'(s), SCO2, CBV, and DPF in the neonatal brain at the bedside in an intensive care unit.


Neuromuscular determinants of simulated occupational performance in career firefighters.
Although firefighters are required to perform various high-intensity critically essential tasks, the influence of neuromuscular function on firefighter occupational performance is unclear. The primary aim of the current study was to identify the key neuromuscular determinants of stair climb (SC) performance in firefighters. Leg extension isometric peak torque (PT), peak power (PP), torque steadiness at 10% (Steadiness10%) and 50% (Steadiness50%) of PT, fatigability following 30 repeated isotonic concentric contractions at 40% of PT, percent body fat (%BF), and a weighted and timed SC task were examined in 41 (age: 32.3 ± 8.2 yrs; %BF: 24.1 ± 7.9%) male career firefighters. Faster SC times (74.7 ± 13.4 s) were associated with greater PT and PP, less fatigability, younger age, and lower %BF (r = -0.530-0.629; P ≤ 0.014), but not Steadiness10% or Steadiness50% (P ≥ 0.193). Stepwise regression analyses indicated that PP and Steadiness50% were the strongest predictors of SC time (R2 = 0.442, P < 0.001). However, when age and %BF were included in the model, these variables became the only significant predictors of SC time (R2 = 0.521, P < 0.001) due to age and %BF being collectively associated with all the neuromuscular variables (excluding Steadiness10%). Lower extremity neuromuscular function, specifically PP and steadiness, and %BF are important modifiable predictors of firefighter SC performance, which becomes increasingly important in aging firefighters.


[Study of hydrodynamic characteristics of artificial heart valves by photochromic imaging].
The paper deals with the hydrodynamics of artificial heart valves (AHVs) used in clinical practice. It reviews and analyzes the studies of AHV hydrodynamics, as well as the hydrodynamic beds which stimulate physiological flow through the valve. Photochronic imaging (PCI) is proposed for examination of AHV hydrodynamic characteristics under model physiological flow. The hydrodynamics of different AHVs was tested on the beds simulating blood flow through AHVs by employing PCI. PCI involved preparation of model photochronic solution that simulates blood, colour labels by using laser radiation. In the model photochronic solution, 10(-6)-10(-9)-sec laser radiation gave rise to linear colour labels whose movement was recorded by a speed camera in the flow behind the valve. The profiles of speed behind the valves, the dimensions of congestive areas, the positions of flow detachment and regurgitation flow were calculated by a speed shooting in different periods of valvular performance. PCI defined congestive areas behind the valves, the areas of closed circulations, the sizes of reversing flow areas and examined the time course of flow behind the valves as a whole. The paper is of interest for AHV designers and cardiac surgeons who apply various AHVs.


High-Resolution Native Mass Spectrometry.
Native mass spectrometry (MS) involves the analysis and characterization of macromolecules, predominantly intact proteins and protein complexes, whereby as much as possible the native structural features of the analytes are retained. As such, native MS enables the study of secondary, tertiary, and even quaternary structure of proteins and other biomolecules. Native MS represents a relatively recent addition to the analytical toolbox of mass spectrometry and has over the past decade experienced immense growth, especially in enhancing sensitivity and resolving power but also in ease of use. With the advent of dedicated mass analyzers, sample preparation and separation approaches, targeted fragmentation techniques, and software solutions, the number of practitioners and novel applications has risen in both academia and industry. This review focuses on recent developments, particularly in high-resolution native MS, describing applications in the structural analysis of protein assemblies, proteoform profiling of─among others─biopharmaceuticals and plasma proteins, and quantitative and qualitative analysis of protein-ligand interactions, with the latter covering lipid, drug, and carbohydrate molecules, to name a few.


Inhibition effects of lamellarin D on human leukemia K562 cell proliferation and underlying mechanisms.
Lamellarin D (LamD) is a marine alkaloid with a pronounced cytotoxicity against a large panel of cancer cells, affecting cell growth and inducing apoptosis. However, the molecular mechanisms of action of this compound are poorly understood. In this study, the anticancer efficacy of LamD was investigated in human leukemia K562 cells. The results showed suppressed cell proliferation and induction of G0/G1-phase arrest,while expression of CDK1, and activity of smad3 and smad5 were reduced, but that of p27, p53 and STGC3 was increased. LamD induced cell apoptosis through activation of caspases-8/-3, inhibition of survivin and Bcl-2, suggesting that this compound may also act through a caspase-independent pathway. Moreover, LamD inhibited the secretion of TGF-β, IL-1β, IL-6, IL-8 and other inflammatory cytokines and the transcriptional activity of transcription factor NF-κB in human leukemia K562 cells. Taken together, our results suggest that LamD-mediated inhibition of leukemia cell proliferation may be related to the induction of apoptosis and the regulation of cell cycle, tumor- related gene expression and cytokine expression, which may provide a new way of thinking for the treatment leukemia.


Timing of emergency interhospital transfers from subacute to acute care and patient outcomes: A prospective cohort study.
Australian and international data show that transfer from inpatient rehabilitation to acute care hospitals occurs in one in ten patients. Early unplanned transfers from subacute to acute care hospitals raises questions about the safety of patient transitions between health sectors. To explore the characteristics of early and late emergency interhospital transfers from subacute to acute care. The investigators defined early transfers as occurring within 1 day and late transfers occurring after 1 day after subacute care admission. This prospective, exploratory cohort study is a subanalysis of data from a larger case-time-control study. Twenty-two wards of eight subacute care hospitals in five major health services in Victoria, Australia. All subacute care hospitals were geographically separate from their health services' acute care hospitals. All patients with an emergency transfer from inpatient rehabilitation or geriatric evaluation and management wards to an acute care hospital within the same health service were included. Patients receiving palliative care were excluded. Data were collected between 22 August 2015 and 30 October 2016 by record audit. To compare patient and admission characteristics between early and late transfers Cochran-Mantel-Haenszel test (CMH) or logistic regression were used to account for health service clustering effect. There were 602 transfers: 54 early (48 patients) and 548 late transfers (505 patients). There was no difference in median age (79.5 vs 80, p = 0.680) or Charlson Comorbidity index (both groups = 3, p = 0.933). Early transfer patients had lower functional independence measure scores on subacute care admission (median 45 vs 66, p < 0.001). Prior to transfer, fewer early transfers had a limitation of medical treatment order in place during their subacute care admission (25.9% vs 48.7%, p < 0.001). The majority of both early and late transfers resulted in acute care hospital readmission (85.1% vs 77.7%, p = 0.204). For patients admitted to acute care, there was no difference in median acute care length of stay (6.5 vs 8 days, p = 0.367). Early transfer patients had fewer in-hospital deaths than late transfer patients (3.8% vs 16.1%, p = 0.004). The high rates of acute care readmission in both groups suggest that transfer was warranted. Early transfer patients had lower in-patient mortality so emergency interhospital transfers, while resource intensive, appear to have a safety benefit. Early transfer patients were less likely than late transfer patients to have limitation of medical treatment orders, so the influence of resuscitation status and patient goals of care on transfer decisions warrants further investigation.


Failure to quantify viral load with two of the three commercial methods in a pregnant woman harboring an HIV type 1 subtype G strain.
The level of HIV-1 RNA in plasma has become one of the most important markers in the follow-up of HIV-infected patients. Three techniques are commercially available: both the Amplicor HIV Monitor and the NASBA HIV-1 RNA QT are target amplification methods, whereas the Quantiplex HIV RNA assay is a branched DNA signal amplification technique. Detection in both target amplification techniques is based on a single primer pair and a single probe in the gag region, whereas multiple probes capture the pol region of the viral RNA in the branched DNA assay. We investigated the discrepant observation of an undetectable viral load in an immunodeficient pregnant HIV-1-infected patient of African origin with no prior antiretroviral treatment. Although clinical progression was present in this patient with tuberculosis and a low CD4 cell count, viral load determinations with both the Amplicor Monitor and NASBA assays revealed no detectable RNA levels. The presence of HIV-1 RNA in the plasma of the patient was demonstrated by an in-house RNA-PCR. Subsequent HIV-1 RNA quantification with the branched DNA method revealed a high viremia (460,000 copies/ml). DNA sequence analysis of the gag gene identified a subtype G HIV-1 strain (HIV-1BL). To our knowledge this is the first report of a patient harboring an HIV-1 genotype of the main group with a high viral load as quantified by the branched DNA assay, but undetectable with the two commercial HIV RNA amplification techniques because of genetic divergence. In the case of discrepant low viral loads determined by one amplification technique in patients with advanced clinical stage one should use an alternative quantification technique for confirmation.


Non-Euclidean properties of spike train metric spaces.
Quantifying the dissimilarity (or distance) between two sequences is essential to the study of action potential (spike) trains in neuroscience and genetic sequences in molecular biology. In neuroscience, traditional methods for sequence comparisons rely on techniques appropriate for multivariate data, which typically assume that the space of sequences is intrinsically Euclidean. More recently, metrics that do not make this assumption have been introduced for comparison of neural activity patterns. These metrics have a formal resemblance to those used in the comparison of genetic sequences. Yet the relationship between such metrics and the traditional Euclidean distances has remained unclear. We show, both analytically and computationally, that the geometries associated with metric spaces of event sequences are intrinsically non-Euclidean. Our results demonstrate that metric spaces enrich the study of neural activity patterns, since accounting for perceptual spaces requires a non-Euclidean geometry.


"Three-propulsion" suspension method for endoscopic thyroid surgery gasless axillary approach.
Gasless endoscopic thyroidectomy through unilateral axillary approach has advantages of clear vision, simple manipulation, short learning curve, hidden surgical incision, no postoperative neck scar, and less swallowing discomfort. During the procedure the separation path goes through thoracic muscle surface, sternocleidomastoid gap and jugular vein, which may meet various variations of neck muscles, blood vessels and nerves. With the "three-propulsion" suspension cavity construction method the procedure advances the dissection from the axillary incision to clavicle, from the clavicle to sternocleidomastoid gap and from the sternocleidomastoid gap to thyroid. Combined with intraoperative hanging upward hook it can establish a good cavity for the subsequent surgical operation. This article introduces the main steps, key points and attentions of the "three-propulsion"suspension cavity construction method in gasless endoscopic thyroidectomy through unilateral axillary approach.


[Anatomo-pathological diagnosis of neonatal malformations of the urinary tract. II. Excreto-urinary tract malformations].
Congenital anomalies of the urinary tract are of great pathological importance and account for about 10.9 per cent of all fetal and neonatal autopsies. This paper reports 17 cases of such lesions compiled from 156 consecutive autopsies of newborn infants performed during 33 months at C.H.R. de Bordeaux. Each malformation is discussed, using embryological classification. These lesions can occur independently but usually they are associated with other organ abnormalities. Whenever, an hereditary syndrome must be seek after. In a first part, we have presented the anomalies of the kidney proper. In a second part, we shall present the anomalies of the excretory apparatus, bladder, and urethra.


Role of Oral Mucosal Fluid and Electrolyte Absorption and Secretion in Dry Mouth.
Dry mouth is induced by dehydration of the oral mucosa, resulting from an imbalance of fluid supply and clearance within the oral cavity. Saliva is the major source of oral mucosal fluid, whereas oral fluid clearance includes evaporation and swallowing. Oral mucosal fluid absorption has been suggested to play a critical role in oral fluid clearance; over-absorption of water and ions across the oral mucosa under certain conditions may be a major component for oral fluid imbalance, leading to mucosal dehydration. While numerous studies have confirmed that the oral mucosa absorbs fluid and electrolytes, the pathways and mechanisms mediating the absorption remain undefined. The transcellular pathway regulating oral mucosal epithelial absorption includes aquaporins, epithelial Na+ channel and/or Na+/H+ exchanger, whereas the paracellular transport is likely to be mediated by tight junctions. The regulatory mechanisms of these pathways require further elucidation. It remains unclear whether the oral mucosa also secretes fluid and ions into the oral cavity. Although intercellular lipids secreted by epithelial cells form the major barrier to paracellular water and ion transport, the role and regulation of these lipids in oral mucosal hydration in physiological and pathological conditions need further investigation. Delineation of these mechanisms will be conducive to the development of preventive and therapeutic interventions for dry mouth.


Lipoleiomyoma With Bizarre Nuclei and Abundant Mast Cells.
Lipoleiomyoma is an uncommon neoplasm of the uterus with a variable incidence in the literature. Histologically, it consists of smooth muscle cells intermixed with mature adipocytes. The histogenesis of this tumor remains obscure and the presence of atypical cells may raise the suspicion of leiomyosarcoma so it is crucial to distinguish between the two. On the other hand, tumor-associated mast cells are being recognized as tumor modulators and potential therapeutic targets. Here, we discuss the case of a 57-year-old female, who presented with a nonspecific symptom of postmenopausal bleeding. She was found to have a large uterine mass and had been treated surgically with a hysterectomy. Histological examination revealed the diagnosis of this uncommon entity. Considering the rarity of the disease, we report this case to add to the existing literature. Furthermore, the significance of these findings is still poorly understood and needs more investigation to fill in the lacking knowledge.


Problems experienced by the informal caregivers of cancer patients and their needs for support.
Informal caregivers experience problems of their own for which they need support, but despite the efforts of the World Health Organization to include the well-being of family members and caregivers in the concept of palliative care, their needs are rarely assessed systematically. This report explores caregivers' problems and their needs for professional support. Seventy-six caregivers of cancer patients with advanced disease completed a comprehensive needs assessment questionnaire, the Problems and Needs in Palliative Care questionnaire-caregiver form, listing 67 potential problems in their quality of life and their role of caregiver and 9 items concerning informational needs. The results of this study reveal that the "Top 20" list of the problems and needs reported by caregivers includes fears and emotional burdens; for the most part, caregivers did not need any more professional attention than they were already receiving. Many, however, needed support for managing patients' symptoms and wanted professional attention for the availability and coordination of services. Despite communalities, there was diversity in caregivers' individual needs. Personal needs could be identified with the Problems and Needs in Palliative Care questionnaire-caregiver form checklist. Although only a few caregivers were affected by some issues, such as financial problems, help for them was often needed. In conclusion, most caregivers would like more professional attention for 4 or 5 specific issues, often related to their competence as caregivers for their patients. Using structured needs assessments with the Problems and Needs in Palliative Care questionnaire-caregiver form seems a feasible method to identify the needs of individual caregivers in palliative care.


[Progress in the study on bone morphogenetic protein 2/4 in central nervous system].
As a member of transforming growth factor β (TGF-β) family, bone morphogenetic proteins (BMPs) are multi-functional factors and play critical roles in heart, cartilage, neural development and postnatal bone formation. It has been demonstrated that among the family, BMP2/4 have been reported to be especially important for the developmental and maturation of central nervous system (CNS). It has different, even opposite functions, in certain given circumstances, which could be a potential risk for BMPs' clinical use.