Preface: Setting the stage for understanding alcohol effects in late aging: A special issue including both human and rodent studies.
It is widely recognized that people worldwide are living longer than in previous decades, with formidable projections regarding the expansion of elderly age groups in the decades to come. Older individuals are also sustaining higher levels of alcohol consumption later in life, and binge drinking remains a prevalent pastime in a significant proportion of aged individuals. Older people are more sensitive to neurobehavioral effects of alcohol, and as individuals age, the cumulative impact of lifetime alcohol intake begins to emerge. This brief review provides a perspective on the emerging field of how alcohol interacts with the aging brain and sets the stage for understanding the relationship between alcohol and overall brain health. In doing so, we introduce a set of articles collected in this book series (all chapters available on PubMed) which spans human epidemiology and clinical outcomes, along with a series of neurobehavioral studies in preclinical (rodent) models. Because both natural aging as well as alcohol use and abuse include tell-tale signs of neuroinflammation (heightened expression of neuroimmune genes, activation of inflammatory signaling pathways, and signs of glial activation), particular emphasis is placed on the role of neuroinflammation in both aging- and alcohol-related alterations in neurobehavioral function, with special emphasis on the spectrum of cognitive dysfunction ranging from mild cognitive impairment to Alzheimer's associated brain pathology.


Efficacy and safety of massage therapy for chronic atrophic gastritis: A protocol for systematic review and meta-analysis.
Chronic atrophic gastritis (CAG) is an established precursor of gastric carcinoma with high prevalence worldwide. It is a typical complex gastro-intestinal disease with multiple influence factors, of which exact mechanisms remain unelucidated. Therefore, an ideal strategy to relieve CAG is urgently needed. In recent years, massage therapy has been increasingly accepted by CAG patients due to its lower costs, fewer unwanted side effects and safety for clinical use. In this systematic review, we aim to evaluate the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating chronic atrophic gastritis: Wanfang and Pubmed Database, China National Knowledge Infrastructure Database, Cochrane Central register of controlled trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to September 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. This proposed study will evaluate the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. The outcomes will include changes in CAG relief and adverse effect. This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.


Meeting 24-h movement guidelines and associations with health related quality of life of Australian adolescents.
This study determined the prevalence of adolescents meeting the individual and combinations of the Australian 24-Hour Movement Guidelines, and their associations with the health related quality of life (HRQoL). The participants were 3096 adolescents (mean age: 12.4 years; 49% female) from wave 7 of the birth-cohort of the Longitudinal Study of Australian Children. The outcome was parent-reported HRQoL. Meeting the 24-Hour Movement Guidelines was defined as: ≥60 min/day of moderate to vigorous physical activity (MVPA), ≤2 hour/day of recreational screen time, and 9-11 hour/night of sleep. Generalised estimating equations were used to examine the associations between meeting vs. not meeting recommendations and HRQoL outcomes. The prevalence of adolescents meeting all three recommendations was 2.4%, with 23% meeting two, and 57% meeting one recommendation. Meeting all three recommendations was associated with higher overall HRQoL score (β = 4.96, 95% CI: 2.54-7.38) as well as physical (β = 5.22, 95% CI: 2.61-7.83) and psychosocial (β = 4.76, 95% CI: 1.77-7.75) scores. Meeting combinations of screen time with MVPA or sleep recommendations were associated with higher scores for all HRQoL outcomes, while meeting MVPA and sleep recommendations was associated with overall HRQoL score. Compared to meeting no recommendation, meeting more recommendations was significantly and incrementally associated with higher scores for all HRQoL outcomes (ptrend<0.001). Overall, meeting more recommendations within the 24-Hour Movement Guidelines was associated with better HRQoL outcomes. However, only a small percentage of adolescents met all the recommendations, which underscores the need for promoting and supporting adherence to these behaviours.


Adaptation of malate dehydrogenase to environmental temperature variability in two populations of Potentilla glandulosa Lindl.
The responses of the kinetic properties of malate dehydrogenase to environmental temperature variability were compared for two populations of Potentilla glandulosa (Rosaceae). The two populations are native to regions of contrasting climates, with the inland population experiencing a high level of temperature variability during growth and the coastal populaton a low level of temperature variability. The substrate binding ability, as measured by apparent K m of both populations was relatively insensitive to assay temperature (Q 10<2.0) over the range of temperatures likely to be encountered during growth. The breadth of this thermal optimum was different for the two populations with the K m of the inland plants exhibiting relative temperature insensitivity over a much wider range of temperatures than the K m of the coastal plants. There was no difference between the two populations in the thermal stability of MDH activity.


Effect of losartan treatment on Smad signaling and recovery from hindlimb unloading-induced soleus muscle atrophy in female rats.
Losartan, an angiotensin II type 1 receptor blocker, exerts protective effect on soleus muscle atrophy in female rats. Thus, we aimed to examine the effect of losartan treatment on the recovery of atrophied soleus muscles. Female Wistar rats were subjected to hindlimb unloading for 7 d and then reloading for 7 d with either phosphate-buffered saline (PBS; n = 9) or losartan (40 mg/kg/day; n = 9). The soleus muscles were removed at rest (sedentary control [SED]; n = 9), after 7 d of hindlimb unloading (HU; n = 9), and after 7 d of reloading (HUR-PBS or HUR-LOS; n = 9 each). The absolute and relative weights, and fiber cross-sectional area (CSA) of the soleus muscles of rats in the HU group were significantly reduced as compared to those of the rats in the SED group at 7 d post-hindlimb unloading. Seven days of reloading significantly increased the muscle weights of rats in the HUR-PBS and HUR-LOS groups, with the recovery rate of the absolute muscle weight and type I fiber CSA being significantly higher in the HUR-LOS group (6.1% and 10.1%, respectively) than in the HUR-PBS group (4.7% and 5.2%, respectively) (p < 0.05). Moreover, the absolute and relative muscle weight in HUR-PBS were lower than SED; however, no significant difference was observed between the SED and HUR-LOS groups. CSAs of type I and IIa fiber were significantly higher in the HUR-LOS group than in the HU group. Losartan administration during reloading resulted in increased Smad1/5/8 and mTOR signaling and decreased Smad2/3 signaling and protein ubiquitination, facilitating the recovery of atrophied soleus muscle. Therefore, losartan administration-induced muscle recovery may partially be attributed to enhanced Smad1/5/8 and mTOR signaling activation, and reduced activation of canonical TGF-β signaling (Smad2/3) in the soleus muscle.


Influence of sampling approach on concentrations of legacy and "novel" brominated flame retardants in indoor dust.
The study investigates the impact of sampling method on the concentrations of PBDEs (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and BDE-209) and NBFRs (PBEB, EH-TBB, BEH-TEBP, BTBPE and DBDPE) in indoor dust. A total of 36 dust samples were collected from 12 homes in Birmingham, UK (3 samples per home comprising researcher collected dust - both RCD from the living room (RCDL) and bedroom (RCDB), with an additional householder vacuum dust sample - HHVD). BDE-209 was the predominant compound, with average concentrations of 2642, 2336 and 2634 ng/g in RCDL, RCDB and HHVD respectively. The next most abundant BFR was BEH-TEBP, followed by DBDPE, with average concentrations of 306, 339 and 233 ng/g for BEH-TEBP and 155, 91 and 152 ng/g for DBDPE in RCDL, RCDB and HHVD respectively. Average concentrations of Σ6tri-hexa-BDEs were 47, 41, and 24 ng/g in RCDL, RCDB and HHVD respectively. With the exception of Σ6tri-hexa-BDEs, BDE-153, BDE-99 and to some extent BEH-TEBP, no significant differences were found between BFR concentrations in RCD and HHVD. Statistically significant correlations were observed between concentrations of Σ6tri-hexa-BDEs, BEH-TEBP and DBDPE in HHVD and in both RCDL and RCDB. However, comparison of estimates of exposure via dust ingestion based on these two sampling methods revealed that using householder vacuum dust underestimates exposure, particularly for Σ6tri-hexa-BDEs, and to some extent for BEH-TEBP. In contrast, HHVD could be a viable alternative to RCD as a metric of exposure for higher brominated BFRs.


Morphometric characteristics of the knee are associated with the injury of the meniscus.
To assess the geometrical risk factors for meniscal injuries. We hypothesized that the narrowness of the intercondylar notch and the smaller tibial spine could increase the risk of meniscal injuries. We retrospectively studied two hundred and seven patients examined for knee magnetic resonance images. Two experienced orthopedists evaluated the severity of meniscal injuries. The notch width, bicondylar notch width, notch width index, condyle width of the femur, tibial spine height, and intercondylar angle were measured in magnetic resonance image slides by two blinded orthopedists. A total of 112 patients with a meniscus injury and 95 patients were as healthy control in all two hundred and seven patients. The NWI (P = 0.027) in patients with meniscus injuries was significantly different from the control group. A 1 SD (0.04 mm) increase in NWI was associated with a 0.4-fold increase in the risk of meniscal injury. A 1 SD (0.04 mm) increase in NWI was associated with a 0.64-fold increase in the risk of grade 3 meniscal injury. Furthermore, NWI and medial spine height are decreased significantly in grade 2 (P < 0.05) meniscal injury than in other grades. The medial spine height was significantly decreased in the meniscal injury group (P = 0.025), and the decrease in medial spine height would increase the risk of meniscal injury (OR = 0.77) and grade 3 meniscal injury (OR = 0.8). The stenosis of the femoral intercondylar notch and small medial tibial spine is risk factors of meniscal injury. The decreased NWI and the medial tibial spine height were also associated with the severity of the meniscal injury.


Detection of bis(2-chlorethyl)-sulfide (Yperite) in urine by high resolution gas chromatography-mass spectrometry.
Bis(2-chlorethyl)-sulfide (Yperite) could be detected by GC/MS in urine samples, concentration ranging from 1 to 30 ppb. These results were supported by high resolution mass spectral data.


Reconstructing reticulate evolutionary histories of plants.
Identifying signatures of hybridization in molecular data and distinguishing them from other causes of phylogenetic incongruence is important for evaluating the evolutionary significance of hybridization in plants. Consensus networks and supernetworks provide a means for doing this. In this review, we explain these methodologies, discuss their potential and illustrate their application with examples from the Brassicaceae.


Scrutiny of the failure of lipid membranes as a function of headgroups, chain length, and lamellarity measured by scanning force microscopy.
A fast, quantitative, and unambiguous screening of material properties of biomembranes using scanning force microscopy in pulsed force mode on lipid membranes is presented. The spatially resolved study of breakthrough force, breakthrough distance, adhesion, stiffness, and topography of lipid membranes as determined simultaneously by digitalized pulsed force mode provides new insight into the structure-function relationship of model membranes, which are systematically analyzed by varying chain length, lipid headgroup, and lamellarity. For this purpose, a novel unbiased analysis method is presented. A strong correlation between adhesion and breakthrough events is found on lipid bilayers and multilayers and discussed in terms of structural stability and chemical and physical interactions. Our findings indicate that multilamellar 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine is mechanically strengthened with respect to material failure by calcium ions in solution.


[The effect of colchicine on liver function tests and hepatic fibrosis in patients with chronic active hepatitis: a study of 3 cases (author's transl)].
Three patients with chronic active hepatitis received Colchicine therapy, as an antifibrotic drug. The effect of this drug is analysed biochemically (serum albumin, total serum billirubin and amino-transferase aspartate) and histologically before and after colchicine therapy. Biochemical improvement was observed. No histological change was noted.


Investigating heartbeat-related in-plane motion and stress levels induced at the aortic root.
The axial motion of aortic root (AR) due to ventricular traction was previously suggested to contribute to ascending aorta (AA) dissection by increasing its longitudinal stress, but AR in-plane motion effects on stresses have never been studied. The objective is to investigate the contribution of AR in-plane motion to AA stress levels. The AR in-plane motion was assessed on magnetic resonance imagining data from 25 healthy volunteers as the movement of the AA section centroid. The measured movement was prescribed to the proximal AA end of an aortic finite element model to investigate its influences on aortic stresses. The finite element model was developed from a patient-specific geometry using LS-DYNA solver and validated against the aortic distensibility. Fluid-structure interaction (FSI) approach was also used to simulate blood hydrodynamic effects on aortic dilation and stresses. The AR in-plane motion was 5.5 ± 1.7 mm with the components of 3.1 ± 1.5 mm along the direction of proximal descending aorta (PDA) to AA centroid and 3.0 ± 1.3 mm perpendicularly under the PDA reference system. The AR axial motion elevated the longitudinal stress of proximal AA by 40% while the corresponding increase due to in-plane motion was always below 5%. The stresses at proximal AA resulted approximately 7% less in FSI simulation with blood flow. The AR in-plane motion was comparable with the magnitude of axial motion. Neither axial nor in-plane motion could directly lead to AA dissection. It is necessary to consider the heterogeneous pressures related to blood hydrodynamics when studying aortic wall stress levels.


Reconfigurable refraction manipulation at synthetic temporal interfaces with scalar and vector gauge potentials.
Photonic gauge potentials, including scalar and vector ones, play fundamental roles in emulating photonic topological effects and for enabling intriguing light transport dynamics. While previous studies mainly focus on manipulating light propagation in uniformly distributed gauge potentials, here we create a series of gauge-potential interfaces with different orientations in a nonuniform discrete-time quantum walk and demonstrate various reconfigurable temporal-refraction effects. We show that for a lattice-site interface with the potential step along the lattice direction, the scalar potentials can yield total internal reflection (TIR) or Klein tunneling, while vector potentials manifest direction-invariant refractions. We also reveal the existence of penetration depth for the temporal TIR by demonstrating frustrated TIR with a double lattice-site interface structure. By contrast, for an interface emerging in the time-evolution direction, the scalar potentials have no effect on the packet propagation, while the vector potentials can enable birefringence, through which we further create a "temporal superlens" to achieve time-reversal operations. Finally, we experimentally demonstrate electric and magnetic Aharonov-Bohm effects using combined lattice-site and evolution-step interfaces of either scalar or vector potential. Our work initiates the creation of artificial heterointerfaces in synthetic time dimension by employing nonuniformly and reconfigurable distributed gauge potentials. This paradigm may find applications in optical pulse reshaping, fiber-optic communications, and quantum simulations.


Synthesis and crystal structure of a PdII complex of ortho-xylylenebis(pyridyl-triazole).
A tetra-dentate ligand, namely, ortho-xylylenebis(pyridyl-triazole), o-xpt, was synthesized using the 'click' method and complexed with Pd(BF4)2. In the title com-plex, bis-{μ-1,1'-(o-xylylene)bis-[4-(pyridin-2-yl)triazole]-κN 3:N 3'}dipalladi-um(II) tetra-kis-(tetrafluoridoborate)-di-methyl-formamide-diethyl ether (1/2/1), as the BF4 salt, and including di-methyl-formamide and diethyl ether solvent mol-ecules, with stoichiometry [Pd2(C22H18N8)2](BF4)4·2C3H7NO·C4H10O, the Pd complex and the disordered diethyl ether mol-ecule lie on inversion centers. The ligand coordinates to the PdII centers with square-planar geometry, forming a dimeric macrocycle. The Pd⋯Pd separation in the complex [Pd2(o-xpt)2]4+ cation is 3.6184 (4) Å. In the crystal, the complex mol-ecules are stacked along the b axis, with π-π inter-actions between the pyridyl-triazole ligands of two mol-ecules.


Phytochemical composition of polar fraction of Stachys germanica L. subsp. salviifolia (Ten.) Gams, a typical plant of Majella National Park.
In this study, we report the isolation and identification of several compounds present in the polar fraction of Stachys germanica L. subsp. salviifolia (Ten.) Gams, collected in the protected area of Majella National Park. In particular, we have isolated and identified harpagide, 7-β-hydroxy-harpagide, ajugol, 5-allosyloxy-aucubin, verbascoside and, for the first time in this genus, arbutin.


Military Acute Concussion Evaluation: A Report on Clinical Usability, Utility, and User's Perceived Confidence.
The signs and symptoms of concussion may not always be clear. Therefore, the Military Acute Concussion Evaluation (MACE) tool was created to help deployed medics and corpsmen identify concussions, particularly in deployed settings. Since 2008, the MACE has been updated multiple times, but each new version of the tool is more complex and takes longer to complete. The objective of this study was to assess the usability, utility, and perceived confidence among military healthcare providers for the latest version, MACE 2. Therefore, a semi-structured interview, including Likert-scale and open-ended questions, was conducted among military healthcare providers at Landstuhl Regional Medical Center in order to assess the usability, utility and perceived confidence of the MACE 2. All of the providers had completed a training course on the MACE 2 and had used it for at least 3 months in their clinics. A total of 28 participants were recruited, including 22 medics, two physicians, three nurses, and one physician assistant. Average scores of usability, utility, and confidence were 5.7, 6.6, and 6.3, respectively, with 7.0 being the most positive score, and thus indicating positive assessments in all categories. The open-ended questions revealed high usability and confidence and the desire for additional training on the tool. In conclusion, despite the increased complexity and duration of the MACE 2 compared with the previous version of this tool, military providers and army medics found the new MACE 2 very useable and had a high degree of confidence in its performance.


Extracellular Volume and Global Longitudinal Strain Both Associate With Outcomes But Correlate Minimally.
This study examined how extracellular volume (ECV) and global longitudinal strain (GLS) relate to each other and to outcomes. Among myriad changes occurring in diseased myocardium, left ventricular imaging metrics of either the interstitium (e.g., ECV) or contractile function (e.g., GLS) may consistently associate with adverse outcomes yet correlate minimally with each other. This scenario suggests that ECV and GLS potentially represent distinct domains of cardiac vulnerability. The study included 1,578 patients referred for cardiovascular magnetic resonance (CMR) without amyloidosis, and it quantified how ECV associated with GLS in linear regression models. ECV and GLS were then compared in their associations with incident outcomes (death and hospitalization for heart failure). ECV and GLS correlated minimally (R2 = 0.04). Over a median follow-up of 5.6 years, 339 patients experienced adverse events (149 hospitalizations for heart failure, 253 deaths, and 63 with both). GLS (univariable hazard ratio: 2.07 per 5% increment; 95% CI: 1.86 to 2.29) and ECV (univariable hazard ratio: 1.66 per 4% increment; 95% CI: 1.51 to 1.82) were principal variables associating with outcomes in univariable and multivariable Cox regression models. Similar results were observed in several clinically important subgroups. In the whole cohort, ECV added prognostic value beyond GLS in univariable and multivariable Cox regression models. GLS and ECV may represent principal but distinct domains of cardiac vulnerability, perhaps reflecting their distinct cellular origins. Whether combining ECV and GLS may advance pathophysiological understanding for a given patient, optimize risk stratification, and foster personalized medicine by targeted therapeutics requires further investigation.


Assessment of outcome after hip fracture: development of a universal assessment system for hip fractures.
The aim of the study was to refine current evaluation systems used to assess outcome after a hip fracture and to devise a simple and practical system to assess all hip fracture patients. Three continuous scales were defined for pain, mobility and functional independence. These were all found to have an acceptable degree of inter-observer agreement. The pre-fracture mobility and independence scores were related to the one-year mortality for a consecutive series of 381 patients. Scores for mobility and functional independence were highly predictive of mortality (p < 0.0001). It is recommended that the outcome after hip fracture should be standardised to these principle outcomes of pain, regain of mobility and independence and mortality. These scores can be use to assess progress and identify those who may require additional assessment or intervention.


Specific spectrophotometric method with trifluoroacetic acid for the determination of selenium(IV) in selenitetriglycerides.
The role of selenium as an antioxidant and anticancer agent is very well documented in the literature. Selenium compound showing the highest activity as a free radicals scavenger and as an anticancer agent should contain selenium at +4 oxidation level. The synthesis of selenitetriglycerides (named selol) was carried out in the Department of Drug Analysis at Warsaw Medical University (Polish Patent 1999). Selenitetriglycerides showed a dimeric structure. In a single dose toxicity studies performed in rats, LD50 was 100 mg Se kg(-1) after oral administration of selol. The subcutaneous and intraperitoneal administration of selol showed extremely low toxicity. The aim of this work was to develop a new specific method for the determination of Se(IV) in selol. We stated that selenitetriglycerides react quantitatively with trifluoroacetic acid (TFA) in dichloromethane giving a red-coloured conjugate. However, recorded spectrum showed the maximum absorption in the wavelength 380 nm. The optimal conditions of the reaction were established, namely temperature 35 degrees C and reaction time 35 min. The reaction was proved to be specific because neither selenites nor other selol constituents react with TFA. The constructed calibration curve obeyed the Lambert-Beer law in the range of 0.1-7.4 mg ml(-1). Molar absorption coefficient is epsilon =9.46 x 10(3) l mol(-1) cm(-1) and epsilon =2.36 x 10(5) l mol(-1) cm(-1) calculated for selenium and selenitetriglyceride dimer (m.w. 1972.72), respectively. Obtained results for selenium determination were confirmed by AAS method. The developed method showed specificity and high sensitivity.


[Prevalence and pattern of distribution of cerebrovascular diseases in 242 hospitalized elderly patients, in a general hospital, autopsied in Belo Horizonte, Minas Gerais, Brazil, from 1976 to 1997].
To describe the prevalence and the types of cerebrovascular diseases (CVDs) in autopsied elderly individuals. Consecutive clinical charts and neuropathological reports of 242 patients aged 61 years or older were reviewed. The patients died in Hospital das Clínicas, Federal University of Minas Gerais, in Belo Horizonte, Minas Gerais, Brazil, from 1976 to 1997. The prevalent diseases of the central nervous system (CNS) found in decreasing order were: CVDs (71.9%), infections (12.4%), neoplasms (7.1%), head trauma (3.7%), nutritional diseases (2.5%) and degenerative diseases (1.7%). The most common CVDs were cerebral atherosclerosis (61.2%), hypertensive cerebrovascular disease (25.6%) and cerebral infarct (14.9%). There was an increase in prevalence and severity of atherosclerosis and an increase in prevalence of hypertensive cerebrovascular disease with advancing age. A significant association between hypertensive cerebrovascular disease and atherosclerosis was found. The CVDs patients had clinical stroke and this was the direct cause of death in 42,7% and 17,3% of the cases, respectively. The CVDs were the most prevalent group of diseases of the CNS in elderly patients. Atherosclerosis and hypertensive cerebrovascular disease were the most common CVDs, and its prevalence increased with advancing age. Hypertensive cerebrovascular disease was significantly associated with atherosclerosis.


Automatic microemulsion preparation for metals determination in fuel samples using a flow-batch analyzer and graphite furnace atomic absorption spectrometry.
The principal thermodynamic advantages of using microemulsions over standard emulsions for flow metal analysis are the greatly increased analyte stability and emulsive homogeneity that improve both the ease of sample preparation, and the analytical result. In this study a piston propelled flow-batch analyzer (PFBA) for the determination of Cu, Cr and Pb in gasoline and naphtha by graphite furnace atomic absorption spectrometry (GF AAS) was explored. Investigative phase modeling for low dilution was conducted both for gasoline and naphtha microemulsions. Rheological considerations were also explored including a mathematical flow derivation to fine tune the system's operational parameters, and the GF AAS coupling. Both manual and automated procedures for microemulsion preparation were compared. The results of the paired t test at a 95% confidence level showed no significant differences between them. Further recovery test results confirmed a negligible matrix effect of the sample on the analyte absorption signals and an efficient stabilization of the samples (with metals) submitted to microemulsion treatment. The accuracy of the developed procedure was attested by good recovery percentages in the ranges of 100.0±3.5% for Pb in the naphtha samples, and 100.2±3.4% and 100.7±4.6% for Cu and Cr, respectively in gasoline samples.


Standardization of orthodontic products--does it make sense?
Since 1994, the DIN (Deutsches Institut für Normung e.V.) has had a German working group named "Orthodontic Products" working toward establishing standardized norms for orthodontic products. In the USA, a similar working group called "Orthodontic Materials" was established in 1996 at the ADA (American Dental Association). Working at the ISO level since 1997, an international team has been in charge of unifying the standards already set at national levels. It is the aim of this article to report on the current state of standardization in Germany and internationally. The standards already published for wires (DIN 13971, ADA Spec. 32), for brackets and tubes (DIN 13971-2, ADA Spec. 100) and for elastomeric elements (DIN 13901) have been considered, as have problems occurring with ISO standards (ISO/CD 15841 and ISO/CD 15841-2) and DIN 13904-1. We demonstrate that the demands made of these products by the orthodontists who use them have lead to reasonable quality standards. Thanks to clearly-defined testing methods, orthodontic products can now be tested and their compliance with these minimum standards can be compared. In fact, the standards that have been agreed upon help both the product manufacturers and their users to improve product quality and, ultimately, the success of orthodontic treatment.


The treatment of chronic depression, part 1: study design and rationale for evaluating the comparative efficacy of sertraline and imipramine as acute, crossover, continuation, and maintenance phase therapies.
Chronic depressions are common, disabling, and undertreated, and prior chronicity predicts future chronicity. However, few studies directly inform the acute or maintenance phase treatments of chronic depressions and even less is known about the effects of treatment on psychosocial functioning. We describe the design and rationale for 2 parallel double-blind, randomized, multicenter acute and maintenance phase treatment trials. One focused on DSM-III-R major depression currently in a chronic (> or = 2 years) major depressive episode, the other on DSM-III-R major depression with concurrent DSM-III-R dysthymia ("double depression"). Considering the critical knowledge deficits, we designed a 12-week acute phase safety and efficacy trial of sertraline versus imipramine, followed by a 16-week continuation treatment phase for subjects with a satisfactory therapeutic response. Patients receiving sertraline who successfully completed the continuation phase entered a 76-week maintenance trial to compare sertraline with placebo; those taking imipramine continued without a placebo substitution. As part of the acute trial, subjects completing but failing to respond to the initial 12-week acute phase medication were crossed over (double-blind) to the alternative medication for a 12-week acute phase trial. We obtained naturalistic follow-up data (up to 18 months) for subjects exiting the protocol at any time. Multiphase protocols for chronic depression can test efficacy by randomized contrasts as well as shed light on key clinical issues such as the degree of response or attrition expected at particular times in a trial or the preferred medication sequence in a potential multistep treatment program.


Effect of midfacial distraction on the obstructed airway in patients with syndromic bilateral coronal synostosis.
Le Fort III osteotomy and midfacial advancement expand the nasopharynx and potentially increase airway dimensions in patients with syndromic bilateral coronal synostosis. Distraction osteogenesis allows greater midfacial advancement, and may offer more improvement in airway obstruction, compared with the conventional 1-stage procedure. This study aimed to document the effect of midfacial distraction-advancement on airway obstruction in patients with syndromic bilateral coronal synostosis. Charts of patients with syndromic bilateral coronal synostosis who had undergone Le Fort III distraction were reviewed. Preoperative and postoperative demographic, cephalometric, polysomnographic, and subjective patient/parental reported data were reviewed. Descriptive and nonparametric bivariate statistics were computed, to document changes in airway parameters. Of 25 patients who underwent midfacial Le Fort III distraction, only 18 had preoperative airway obstruction. The mean age at operation for patients with airway obstruction was (+/-SD) 10.4 +/- 4.2 years (range, 2.7 to 17.4 years), and the average advancement was 20.5 +/- 7.4 mm (range, 10 to 30 mm). Five of 6 patients with a tracheostomy were decannulated; 1 patient had persistent central apnea that prevented decannulation. The mean respiratory distress index for the group improved from 33.4 +/- 37.57 (range, 1.8 to 109.2) to 12.6 +/- 26.32 (range, 0.00 to 72.0) (P < .05). Six of 9 patients no longer required continuous or bilevel positive airway pressure. All patients reported decreased snoring (P < .05). Midfacial distraction improves airway obstruction in patients with syndromic bilateral coronal synostosis. Clinicians can counsel patients and families that this procedure usually permits decannulation and discontinuation of continuous or bilevel positive airway pressure.


Isolated true parachute mitral valve in an asymptomatic elderly patient.
We report the extremely rare case of a 73-year-old asymptomatic patient who has an isolated true parachute mitral valve (PMV). In the echocardiographic examination, the parasternal long-axis view showed a single papillary muscle. The short-axis view revealed the presence of a symmetric mitral valve orifice with all chordae attaching to a large anterolateral papillary muscle. Because detailed examination did not reveal the presence of other complications, this patient was diagnosed as an isolated true PMV.


Investigating the Chronology of Meniscus Root Tears: Do Medial Meniscus Posterior Root Tears Cause Extrusion or the Other Way Around?
Meniscus root tears are increasingly being recognized. Meniscal extrusion has previously been associated with medial root tears; however, the relationship between secondary meniscal restraints, such as the meniscotibial (MT) ligament, extrusion, and root tears has yet to be formally evaluated. To better understand the association between MT ligament competence, medial meniscal extrusion, and medial meniscus posterior root tears (MMPRTs) as well as to determine the progression of meniscal extrusion over time. Case series; Level of evidence, 4. Serial magnetic resonance imaging (MRI) scans were reviewed for patients who showed evidence of medial meniscal extrusion and MMPRTs on at least 1 of ≥2 available MRI scans. All patients were symptomatic at the time of diagnosis. All MRI scans were analyzed independently by 2 board-certified musculoskeletal radiologists. MT ligament disruption, medial meniscal extrusion, and MMPRTs were recorded for each MRI scan. The time between MRI scans, presence of insufficiency fractures, and Outerbridge classification for the medial femur and tibia were also evaluated. Overall, 27 knees in 26 patients were included in this study, with a total of 63 MRI scans analyzed (21 knees with 2 MRI scans, 3 with 3 MRI scans, and 3 with 4 MRI scans). All patients demonstrated clear medial meniscal extrusion and MT ligament disruption before the subsequent development of MMPRTs (P < .001). Mean extrusion at the time of initial MRI was 3.3 ± 1.1 mm and increased significantly to 5.5 ± 1.8 mm at the time of first imaging with an identified MMPRT (P < .001). The mean time between initial MRI and the first identification of an MMPRT on later MRI was 1.7 ± 1.6 years. In a sample of 27 symptomatic knees with serial MRI scans both before and after an MMPRT diagnosis, all patients demonstrated MT ligament disruption and associated meniscal extrusion before the development of subsequent medial meniscus root tears. These findings suggest that MT ligament disruption and medial meniscal extrusion represent early and predisposing events contributing to MMPRTs. Therefore, this provides a possible explanation of why meniscal extrusion is not corrected with medial meniscus root repair.


Lateral lumbar interbody fusion in adult spine deformity - A review of literature.
Surgery for adult spine deformity presents a challenging issue for spinal surgeons with high morbidity rates reported in the literature. The minimally invasive lateral approach aims at reducing these complications while maintaining similar outcomes as associated with open spinal surgeries. The aim of this paper is to review the literature on the use of lateral lumbar interbody fusion in the cases of adult spinal deformity. A literature review was done using the healthcare database Advanced Research on NICE and NHS website using Medline. Search terms were "XLIF" or "LLIF" or "DLIF" or "lateral lumbar interbody fusion" or "minimal invasive lateral fusion" and "adult spinal deformity" or "spinal deformity". A total of 417 studies were considered for the review and 44 studies were shortlisted after going through the selection criteria. The data of 1722 patients and 4057 fusion levels were analysed for this review. The mean age of the patients was 65.18 years with L4/5 being the most common level fused in this review. We found significant improvement in the radiological parameters (lordosis, scoliosis, and disk height) in the pooled data. Transient neurological symptoms and cage subsidence were the two most common complications reported. LLIF is a safe and effective approach in managing adult spinal deformity with low morbidity and acceptable complication rates. It can be used alone for lower grades of deformity and as an adjuvant procedure to decrease the magnitude of open surgeries in high-grade deformities.


Effect of a combination of deoxynivalenol and nivalenol on lipopolisaccharide-induced nitric oxide production by mouse macrophages.
Deoxynivalenol (DON) and nivalenol (NIV) are trichothecene mycotoxins produced by Fusarium fungi as secondary metabolites. Both compounds have the immunotoxic effects that the productions of inflammatory mediators by activated macrophages is disturbed. Co-contamination with DON and NIV can occur; however, the effects of simultaneous contamination are not well known. The present study investigated the combined effects of DON and NIV on nitric oxide (NO) production by mouse macrophages stimulated with lipopolisaccharide (LPS). The inhibitory effect of DON and NIV on NO release from activated macrophages has already been reported as an appropriate indicator of immunotoxic effect of the both compounds. LPS-induced NO production in macrophages was inhibited by both of these toxins individually in a dose-dependent manner, and toxin mixtures at the same concentration inhibited NO production in the same manner. In addition, there were no unique inhibitory effects on LPS-induced NO production in macrophages in the presence of mixtures of various molar ratios. These results suggest that the combined effects of DON and NIV can be predicted based on addition of each compound alone.


Robotic Kinematic measures of the arm in chronic Stroke: part 2 - strong correlation with clinical outcome measures.
A detailed sensorimotor evaluation is essential in planning effective, individualized therapy post-stroke. Robotic kinematic assay may offer better accuracy and resolution to understand stroke recovery. Here we investigate the added value of distal wrist measurement to a proximal robotic kinematic assay to improve its correlation with clinical upper extremity measures in chronic stroke. Secondly, we compare linear and nonlinear regression models. Data was sourced from a multicenter randomized controlled trial conducted from 2012 to 2016, investigating the combined effect of robotic therapy and transcranial direct current stimulation (tDCS). 24 kinematic metrics were derived from 4 shoulder-elbow tasks and 35 metrics from 3 wrist and forearm evaluation tasks. A correlation-based feature selection was performed, keeping only features substantially correlated with the target attribute (R > 0.5.) Nonlinear models took the form of a multilayer perceptron neural network: one hidden layer and one linear output. Shoulder-elbow metrics showed a significant correlation with the Fugl Meyer Assessment (upper extremity, FMA-UE), with a R = 0.82 (P < 0.001) for the linear model and R = 0.88 (P < 0.001) for the nonlinear model. Similarly, a high correlation was found for wrist kinematics and the FMA-UE (R = 0.91 (P < 0.001) and R = 0.92 (P < 0.001) for the linear and nonlinear model respectively). The combined analysis produced a correlation of R = 0.91 (P < 0.001) for the linear model and R = 0.91 (P < 0.001) for the nonlinear model. Distal wrist kinematics were highly correlated to clinical outcomes, warranting future investigation to explore our nonlinear wrist model with acute or subacute stroke populations. http://www.clinicaltrials.gov . Actual study start date September 2012. First registered on 15 November 2012. Retrospectively registered. Unique identifiers: NCT01726673 and NCT03562663 .


Biosorption of the strontium ion by irradiated Saccharomyces cerevisiae under culture conditions.
As a new-emerging method for strontium disposal, biosorption has shown advantages such as high sorption capacity; low cost. In this study, we investigated the potential of Saccharomyces cerevisiae (S. cerevisiae) in strontium disposal under culture conditions and the effects of irradiation on their biosorption capabilities. We found that S. cerevisiae can survive irradiation and grow. Pre-exposure to irradiation rendered S. cerevisiae resistant to further irradiation. Surprisingly, the pre-exposure to irradiation can increase the biosorption capability of S. cerevisiae. We further investigated the factors that influenced the biosorption efficiency, which were (strongest to weakest): pH > strontium concentration > time > temperature. In our orthogonal experiment, the optimal conditions for strontium biosorption by irradiated S. cerevisiae were: pH 7, 150 mg L-1 strontium at the temperature of 32 °C with 30 h. The equilibrium of strontium biosorption was analyzed by Langmuir and Freundlich models, from which the formal model is found to provide a better fit for the experimental results. The kinetics of strontium biosorption by living irradiated S. cerevisiae was found to be comprised of three phases: dramatically increased during 0-9 h, decreased during 12-24 h, and increased during 30-50 h. These results provide a systematic understanding of the biosorption capabilities of irradiated S. cerevisiae, which can contribute to the development of remediating nuclear waste water.


Limitations of Nerve Fiber Density as a Prognostic Marker in Predicting Oncological Outcomes in Hepatocellular Carcinoma.
It has been shown that the presence and density of nerve fibers (NFs; NFD) in the tumor microenvironment (TME) may play an important prognostic role in predicting long-term oncological outcomes in various malignancies. However, the role of NFD in the prognosis of hepatocellular carcinoma (HCC) is yet to be explored. To this end, we aimed to investigate the impact of NFs on oncological outcomes in a large European single-center cohort of HCC patients. In total, 153 HCC patients who underwent partial hepatectomy in a curative-intent setting between 2010 and 2021 at our university hospital were included in this study. Group comparisons between patients with and without NFs were conducted and the association of recurrence-free survival (RFS) and overall survival (OS) with the presence of NFs and other clinico-pathological variables were determined by univariate and multivariable Cox regression models. Patients with NFs in the TME presented with a median OS of 66 months (95% CI: 30−102) compared to 42 months (95% CI: 20−63) for patients without NFs (p = 0.804 log-rank). Further, RFS was 26 months (95% CI: 12−40) for patients with NFs compared to 18 months (95% CI: 9−27) for patients without NFs (p = 0.666 log-rank). In a subgroup analysis, patients with NFD ≤ 5 showed a median OS of 54 months (95% CI: 11−97) compared to 48 months (95% CI: 0−106) for the group of patients with NFD > 5 (p = 0.787 log-rank). Correspondingly, the RFS was 26 months (95% CI: 10−42) in patients with NFD ≤ 5 and 29 months (95% CI: 14−44) for the subcohort with NFD > 5 (p = 0.421 log-rank). Further, group comparisons showed no clinico-pathological differences between patients with NFs (n = 76) and without NFs (n = 77) and NFs were not associated with OS (p = 0.806) and RFS (p = 0.322) in our Cox regression models. In contrast to observations in various malignancies, NFs in the TME and NFD are not associated with long-term oncological outcomes in HCC patients undergoing surgery.


Ion channel activity of the CSFV p7 viroporin in surrogates of the ER lipid bilayer.
Viroporins comprise a family of non-structural proteins that play significant and diverse roles during the replication cycle of many animal viruses. Consequently, they have become promising targets for inhibitory drug and vaccine development. Structure–function traits common to all members of the family are their small size (ca. 60–120 aa), high hydrophobicity, and the presence of helical domains that transverse the membrane and assemble into oligomeric-permeating structures therein. The possibility that viroporins show in particular conditions any kind of specificity in the transport of ions and small solutes remains a point of contention in the field. Here we have approached this issue using the Classical Swine Fever Virus (CSFV) protein p7 viroporin as a model. We have previously reported that CSFV-p7 induces release of ANTS (MW: 427.33) from lipid vesicles that emulate the Endoplasmic Reticulum (ER) membrane, and that this process is dependent on pH, modulated by the lipid composition, and recreated by a C-terminal transmembrane helix. Here we have assayed CSFV-p7 for its capacity to form ion-conducting channels in ER-like planar lipid membranes, and established whether this activity is subject to regulation by the same factors. The analysis of electrophysiological recordings in ER membrane surrogates suggests that CSFV-p7 forms pores wide enough to allow ANTS release. Moreover, we were able to discriminate between two pore structures with slightly different sizes and opposite ion selectivities. The fact that the relative abundances of each pore type depend crucially on membrane composition strengthens the view that the physicochemical properties of the lipid bilayers present in the cell endomembrane system modulate viroporin activity.


Helping methods used by nurses in a psychiatric hospital environment.
This qualitative study aims to describe the helping methods used by psychiatric nurses in a hospital environment from as evidenced by video observations and nurses' and patients' descriptions. The data, which were collected by videotaping different nursing situations and by interviewing the nurses and patients afterwards, consisted of 520 pages of written text. A total of 569 utterances were extracted from the text to describe the helping methods used in psychiatric nursing. Each utterance constituted a classification unit. Deductive content analysis techniques were used to analyze the data. The results obtained from the nurses' and patients' descriptions and the videotaped episodes showed that the most commonly used helping methods were of the confirmatory kind (50%), while educational methods came second (37%) and catalytic methods third (13%).


Assessing the double phonemic representation in bilingual speakers of Spanish and English: an electrophysiological study.
Event Related Potentials (ERPs) were recorded from Spanish-English bilinguals (N=10) to test pre-attentive speech discrimination in two language contexts. ERPs were recorded while participants silently read magazines in English or Spanish. Two speech contrast conditions were recorded in each language context. In the phonemic in English condition, the speech sounds represented two different phonemic categories in English, but represented the same phonemic category in Spanish. In the phonemic in Spanish condition, the speech sounds represented two different phonemic categories in Spanish, but represented the same phonemic categories in English. Results showed pre-attentive discrimination when the acoustics/phonetics of the speech sounds match the language context (e.g., phonemic in English condition during the English language context). The results suggest that language contexts can affect pre-attentive auditory change detection. Specifically, bilinguals' mental processing of stop consonants relies on contextual linguistic information.


Genome-wide RNAi screens in bloodstream form trypanosomes identify drug transporters.
An inducible RNA interference (RNAi) library, consisting of a pool of independent stable transformants with 9-fold genome coverage, was constructed in bloodstream form Trypanosoma brucei using an improved transfection protocol. RNAi induction and selection of resistant parasites was performed in the presence of melarsoprol or eflornithine. The former led to the isolation of the adenosine transporter TbAT1, which is known to be involved in melarsoprol uptake, while the latter identified an amino acid transporter, AAT6. Knockdown of AAT6 reduced mRNA levels to 30-35% in independent clones and increased resistance to eflornithine >5-fold. Genome-wide screens with this library allow an unbiased approach to gene discovery, are extremely rapid and do not exclude essential genes.


Effects of Sleep Fragmentation on White Matter Pathology in a Rat Model of Cerebral Small Vessel Disease.
Mounting evidence indicated the correlation between sleep and cerebral small vessel disease (CSVD). However, little is known about the exact causality between poor sleep and white matter injury, a typical signature of CSVD, as well as the underlying mechanisms. Spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats were subjected to sleep fragmentation for 16 weeks. The effects of chronic sleep disruption on the deep white matter and cognitive performance were observed. SHR were validated as a rat model for CSVD. Fragmented sleep induced strain-dependent white matter abnormalities, characterized by reduced myelin integrity, impaired oligodendrocytes precursor cells (OPC) maturation and pro-inflammatory microglial polarization. Partially reversible phenotypes of OPC and microglia were observed in parallel following sleep recovery. Long-term SF induced pathological effects on the deep white matter in a rat model of CSVD. The pro-inflammatory microglial activation and the block of OPC maturation may be involved in the mechanisms linking sleep to white matter injury.


Regulation of glycogen synthase kinase 3beta functions by modification of the small ubiquitin-like modifier.
Modification of the Small Ubiquitin-like Modifier (SUMO) (SUMOylation) appears to regulate diverse cellular processes, including nuclear transport, signal transduction, apoptosis, autophagy, cell cycle control, ubiquitin-dependent degradation and gene transcription. Glycogen synthase kinase 3beta (GSK 3beta) is a serine/threonine kinase that is thought to contribute to a variety of biological events, including embryonic development, metabolism, tumorigenesis, and cell death. GSK 3beta is a constitutively active kinase that regulates many intracellular signaling pathways by phosphorylating substrates such as beta-catenin. We noticed that the putative SUMOylation sites are localized on K(292 )residueof (291)FKFPQ(295) in GSK 3beta based on analysis of the SUMOylation consensus sequence. In this report, we showed that the SUMOylation of GSK 3beta occurs on its K(292) residue, and this modification promotes its nuclear localization in COS-1. Additionally, our data showed that the GSK 3beta SUMO mutant (K292R) decreased its kinase activity and protein stability, affecting cell death. Therefore, our observations at first time suggested that SUMOylation on the K(292) residue of GSK 3beta might be a GSK 3beta regulation mechanism for its kinase activation, subcellular localization, protein stability, and cell apoptosis.


Rat cardiomyocyte H9c2(2-1)-based sulforhodamine B assay as a promising in vitro method to assess the biological component of effluent toxicity.
The treatment of wastewaters is crucial to maintain the ecological status of receiving waters, and thereby guarantee the protection of aquatic life and human health. Wastewater quality evaluation is conventionally based on physicochemical parameters, but increasing attention has been paid to integrate physicochemical and biological data. Nevertheless, the regulatory use of fish in biological testing methods has been subject to various ethical and cost concerns, and in vitro cell-based assays have thus become an important topic of interest. Hence, the present study intends: (a) to evaluate the efficiency of two different sample pre-concentration techniques (lyophilisation and solid phase extraction) to assess the toxicity of municipal effluents on rat cardiomyoblast H9c2(2-1) cells, and (b) maximizing the use of the effluent sample collected, to estimate the environmental condition of the receiving environment. The gathered results demonstrate that the H9c2(2-1) sulforhodamine B-based assay is an appropriate in vitro method to assess biological effluent toxicity, and the best results were attained by lyophilising the sample as pre-treatment. Due to its response, the H9c2(2-1) cell line might be a possible alternative in vitro model for fish lethal testing to assess the toxicity of municipal effluents. The physicochemical status of the sample suggests a high potential for eutrophication, and iron exceeded the permissible level for wastewater discharge, possibly due to the addition of ferric chloride for wastewater treatment. In general, the levels of carbamazepine and sulfamethoxazole are higher than those reported for other countries, and both surpassed the aquatic protective values for long-term exposure.


Chromium-51 dosimetry of lymphocytes labeled incidentally during nuclear medicine procedures.
Conventional dosimetry based on MIRD procedure fails to consider the localized energy deposition from the radionuclides decaying by the emission of Auger electrons. The cellular dosimetry of human peripheral blood lymphocytes labeled with 51 Cr, an Auger electron emitter, was calculated. Conventional dosimetric calculations reveal a dose of 0.024-0.17 rad/h/tube. In contrast the lymphocyte dose ranged from 0.053-0.339 rad/h with projected cumulative values of 51-324 rad for surviving lymphocytes.


Sex-related differences in hematological values. A study on the erythrocyte and granulocyte count, plasma iron and iron-binding proteins in human transsexuals on contrasexual hormone therapy.
Hematological data known or supposed to be influenced by individual sex hormones were evaluated in 18 untreated transsexuals (TS) and in 20 castrated or non-castrated TS on androgen and estrogen treatment, respectively. Profiting from a situation of clinically controlled hormonal sex-transformation it was tested, whether the circulating erythrocyte and granulocyte mass and iron metabolism are linked to a male and female sex-hormone constellation. The erythrocyte and granulocyte counts were significantly higher in untreated males and treated female-to-male TS than in untreated females and treated male-to-female TS. The unexpected finding of sex hormone-dependent granulocyte fluctuations was corroborated by parallel concentration changes of lactoferrin, a granulocyte-derived plasma protein. Iron metabolism as judged from plasma iron, total iron-binding capacity and serum ferritin was unaffected by sexual transformation. Plasma iron and the total iron-binding capacity did not differ significantly in untreated and treated TS of either type. The serum ferritin concentration, however, was significantly lower in untreated as well as in virilized females than in untreated and in feminized males, but was not significantly changed by long-term androgen or estrogen treatment. The present study demonstrates the potential of human transsexualism as a model for the study of sex-related biological processes.


Effectiveness and Safety of Oral Propranolol versus Other Treatments for Infantile Hemangiomas: A Meta-Analysis.
Epidemiological studies evaluating treatments for infantile hemangiomas have produced inconsistent results. A meta-analysis of published data was conducted to investigate the effectiveness and safety of oral propranolol versus other treatments for infantile hemangiomas. A meta-analysis was conducted based on literature (published from 1960 to December 1, 2014) found on the PubMed, EMBASE, and OVID search engines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the outcome measures. Heterogeneity, publication bias and subgroup analysis were performed. A total of 61 studies involving 5,130 participants met the inclusion criteria. Propranolol was found to be a more effective modality in treating IHs (ORs = 0.92; 95%CI, 0.89-0.95) and had fewer complications compared to the other treatments including systemic steroids (ORs = 0.68; 95% CI, 0.59-0.76); laser ablation (ORs = 0.55; 95% CI, 0.43-0.67); other beta-adrenergic blockers (ORs = 0.56; 95% CI, 0.50-0.61) and surgery (ORs = 0.55; 95% CI, 0.28-0.81). A subgroup analysis of propranolol showed that a dose of 2 mg/kg/day or more yielded better outcomes (ORs = 0.92; 95% CI, 0.88-0.95; ORs = 0.95; 95% CI, 0.89-1.00), and IHs that had not been previously treated had better responses to propranolol treatment (ORs = 0.95; 95% CI, 0.91-0.98). The meta-analysis demonstrated that propranolol was more effective and safer than other therapies in treating IHs. It provides strong evidence for supporting the use of propranolol as a first-line therapy for IHs.


Molecular cloning, characterization, and expression analysis of a heat shock protein (HSP) 70 gene from Paphia undulata.
In this study, a full-length HSP70 cDNA from Paphia undulata was cloned using reverse transcriptase polymerase chain reaction (RT-PCR) coupled with rapid amplification of cDNA ends (RACE). The full-length cDNA is 2,351 bp, consisting of a 5'-untranslated region (UTR) of 83 bp, a 3'-UTR of 315 bp, and an open reading frame (ORF) of 1,953 bp. This cDNA encodes 650 amino acids with an estimated molecular weight of 71.3 kDa and an isoelectric point of 5.51. Based on the amino acid sequence analysis and phylogenetic analysis, this HSP70 gene was identified as a member of the cytoplasmic HSP70 family, being the constitutive expression, and it was designated as PuHSC70. The distribution of PuHSC70 mRNA in the mantle, digestive gland, adductor muscle, gonad, gill, heart, and hemocytes suggested that PuHSC70 is ubiquitously expressed. The mRNA levels of PuHSC70 under high temperature and high salinity stresses were analyzed by real-time PCR. Under high temperature stress of 32°C, PuHSC70 mRNA in the mantle, digestive gland, gill, and heart was significantly up-regulated at 1h and 2h, and it was then progressively down-regulated. In the adductor muscle, the level of PuHSC70 mRNA gradually increased throughout the study period; the mRNA levels in the gonad and hemocytes increased significantly at 4h and 8h (P<0.05) and then decreased at 8h and 14 h, respectively, however they increased again afterwards, reaching the highest levels at 50h. Under high salinity (32 ‰) stress, the mRNA levels of PuHSC70 in the mantle and gonad were increased significantly only at 24h and 48 h (P<0.05), and at the rest of the study period they were slightly elevated. Compared with the pretreatment level, the levels of expression in the digestive gland and gill were unchanged or reduced throughout the study period. The levels of PuHSC70 mRNA in the adductor muscle, hemocytes, and heart were significantly increased, reaching a maximum at 24h, and then they gradually decreased; moreover, in the heart, the mRNA expression recovered to the pretreatment level at 50h; while in the adductor muscle and hemocytes, the expression level remained higher than that of the control. The cloning and expression analyses of PuHSC70 provide theoretical basis to further study the mechanism of physiological response to thermal and high salinity stresses.


Diagnosis and treatment of feto-maternal hemorrhage in a fetus with homozygous von Willebrand's disease.
In a fetus with severe type-III von Willebrand's disease, fetal blood sampling by cordocentesis was associated with feto-maternal hemorrhage, fetal hypovolemia, and persistent bradycardia. The fetal condition improved after intracardiac transfusion of blood.


Precise Identification and Profiling of Surface Proteins of Ultra Rare Tumor Specific Extracellular Vesicle with Dynamic Quantitative Plasmonic Imaging.
Specific detection of tumor-derived EVs (tEVs) in plasma is complicated by nontumor EVs and non-EV particles. To accurately identify tEVs and profile their surface protein expression at single tEV resolution directly with clinical plasma is still an unmet need. Here, we present a Dynamic Immunoassay for Single tEV surface protein Profiling (DISEP), a kinetic assay based on surface plasmon resonance microscopy (SPRM) for specific single tEV profiling. DISEP adopts a pair of low-affinity oligonucleotide probes to respectively label EV surface proteins and functionalize an SPRM biosensor interface. tEVs labeled with the oligonucleotide probes possess distinctive binding kinetics from nonspecific particles in plasma, which permits accurate digital plasmonic counting of single EVs. We demonstrate DISEP for recognizing target EVs among 350-fold background plasma particles with high sensitivity (4677 EVs per μL). Clinical plasma samples were analyzed to discriminate between pancreatic cancer patients (n = 40) and healthy donors (n = 45). With a panel of biomarker signatures (EpCAM, HER2, and GPC1), DISEP only requires 10 μL primary sample from each donor to classify tumor patients with an area under the curve of 0.98. DISEP provides a highly specific EV detection and surface protein profiling strategy for early cancer diagnosis.


[Changes in the metabolism of adenine-containing components in the heart during experimental myocardial infarct].
Turnover of heart polynucleotides, adenine nucleotides and adenosine was studied in dynamics of dog experimental myocardial infarction. In the areas of necrosis an inhibition of RNAase and DNAase was observed and later on - an activation of these enzymes with simultaneous increase in content of RNA and DNA; the stable decrease in ATP and ADP content was also found but content of AMP remained at the initial level. Conversion of AMP into adenosine was limited due to inhibition of 5-nucleotidase, whereas the direct AMP deamination and degradation of adenosine proceeded with the normal rate. Out of the necrosis area 5-nucleotidase maintained the high activity but both "non-adenosine" pathway of AMP degradation and adenosine splitting were inhibited; this promoted the nucleoside formation and maintained its level in the tissue. Alterations in content of RNA, DNA and adenine mononucleotides out of the infarction area were similar to the alterations in the impaired zone but less distinct and stable.


Demonstration of a microwave spectrum analyzer based on time-domain optical processing in fiber.
We demonstrate a novel method for spectral analysis of microwave signals that employs time-domain processing in fiber. We use anomalous dispersion in single-mode fiber to perform a Fresnel transform followed by a matched amount of dispersion-compensating fiber to perform an inverse Fresnel transform of an ultrashort pulse. After the Fresnel-transformed waveform is modulated by the microwave signal, the waveform at the output of the dispersion-compensating fiber represents the ultrashort pulse convolved with the microwave spectrum. An experimental system for spectral analysis of microwave signals in the range 6-21 GHz is demonstrated.


Identification of Prognostic Markers of Gynecologic Cancers Utilizing Patient-Derived Xenograft Mouse Models.
Patient-derived xenografts (PDXs) are important in vivo models for the development of precision medicine. However, challenges exist regarding genetic alterations and relapse after primary treatment. Thus, PDX models are required as a new approach for preclinical and clinical studies. We established PDX models of gynecologic cancers and analyzed their clinical information. We subcutaneously transplanted 207 tumor tissues from patients with gynecologic cancer into nude mice from 2014 to 2019. The successful engraftment rate of ovarian, cervical, and uterine cancer was 47%, 64%, and 56%, respectively. The subsequent passages (P2 and P3) showed higher success and faster growth rates than the first passage (P1). Using gynecologic cancer PDX models, the tumor grade is a common clinical factor affecting PDX establishment. We found that the PDX success rate correlated with the patient's prognosis, and also that ovarian cancer patients with a poor prognosis had a faster PDX growth rate (p < 0.0001). Next, the gene sets associated with inflammation and immune responses were shown in high-ranking successful PDX engraftment through gene set enrichment analysis and RNA sequencing. Up-regulated genes in successful engraftment were found to correlate with ovarian clear cell cancer patient outcomes via Gene Expression Omnibus dataset analysis.


Apparent antioxidant effect of l-deprenyl on hydroxyl radical formation and nigral injury elicited by MPP+ in vivo.
Using a modified microdialysis procedure, we confirmed that intrastriatal administration of 1-methyl-4-phenylpyridinium ion (MPP+) induced a sustained overflow of dopamine accompanied by increased formation of hydroxyl free radicals (.OH) as reflected by salicylate hydroxylation. Pretreatment with l-deprenyl (selegiline 60 pmol, intrastriatal perfusion) significantly decreased the .OH formation elicited by MPP+ (75 nmol). There was a small decrease of dopamine efflux and an insignificant change of the ratio of 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine following l-deprenyl pretreatment. These in vivo findings support prior in vitro data that an unique antioxidant property of l-deprenyl may be independent of its inhibition of type B monoamine oxidase. In addition, intranigral co-administration of l-deprenyl (4.2 nmol) with MPP+ (4.2 nmol) completely protected nigral neurons from probable oxidative injuries induced by MPP+ (4.2 nmol), as reflected by a near 50% loss of striatal dopamine ipsilateral to the side of infusion of drug into the substantia nigra. This apparent neuroprotective effect of l-deprenyl on midbrain nigral neurons was also confirmed by histological findings. The present in vivo data clearly demonstrate that l-deprenyl can protect nigral neurons against dopamine neurotoxicity produced by MPP+, as suggested by an earlier in vitro study. Thus, l-deprenyl can preserve the function of MPP(+)-damaged nigral neurons perhaps by its apparent antioxidant property in addition to its blockade of the bioactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium metabolites by type B monoamine oxidase.


Validation of a gas chromatography-mass spectrometry isotope dilution method for the determination of 2-butoxyethanol and other common glycol ethers in consumer products.
A gas chromatography-mass spectrometry isotope dilution (GC-MS ID) method was developed and tested for the determination of 14 common glycol ethers in consumer products. Stable isotope labelled standards, 2-methoxyethanol-D(7) and 2-butoxyethanol-(13)C(2) (CDN isotopes) were employed to enhance the accuracy and precision of the glycol ethers determination. A 1000-fold sample dilution with methanol was applied to avoid column overload and contamination. At this dilution matrix effects were in most cases negligible and did not interfere with the analysis. The instrument detection limit (IDL) for analysed compounds varied from 0.01 to 1 μg/mL; while the estimated limit of quantification (LoQ) varied between different glycol ethers from 0.02 to 3.4 μg/mL. Calibration was tested in the range of 0.1-200 μg/mL and showed that the linear fit is upheld from 0.1 to 10 μg/mL, and extends beyond this range for some of the analytes. Recoveries of glycol ethers from products with different matrices were similar. The recoveries varied from 87% to 116% between the analysed compounds, while measurements precision varied between 2% and 14%. The method is applicable to products with glycol ether concentrations above 0.002-0.2% (w/w). The concentration range can be extended below the specified limits by decreasing the dilution factor; however, with lower dilution the sample matrix effect is expected to be stronger. Products with very high concentrations of glycol ether (>20%) may need to be further diluted prior to injection to avoid column overload. The method can be used for testing liquid and aerosol products designed for household use, such as cleaners, paints, solvents and paint stripers, for compliance and enforcement of regulations which limit glycol ethers content.


DYNC1H1 regulates NSCLC cell growth and metastasis by IFN-γ-JAK-STAT signaling and is associated with an aberrant immune response.
It is urgent to identify new biomarkers and therapeutic targets to ameliorate the clinical prognosis of patients with lung cancer. The functional significance and molecular mechanism of dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) in nonsmall cell lung cancer (NSCLC) progression is still elusive. In our current study, publicly available data and Western blotting experiments confirmed that DYNC1H1 expression was upregulated in lung cancer samples compared with noncancerous samples. Quantitative real-time PCR (qPCR) results indicated that high DYNC1H1 expression in lung cancer tissues was significantly associated with clinical tumor stage and distal metastasis; moreover, its high expression was negatively correlated with prognosis. Functional experiments demonstrated that DYNC1H1 loss of function caused a significant decrease in cell viability and cell proliferative ability, inhibition of the cell cycle, and promotion of both migration potential and invasion potential in vitro. Animal experiments by tail vein injection of lung cancer cells showed that DYNC1H1 knockdown significantly decreased lung cancer metastasis. Mechanistically, the results from a human protein array showed changes in the IFN-γ-JAK-STAT signaling pathway, and analysis of The Cancer Genome Atlas (TCGA) immune data demonstrated that disturbance of the immune microenvironment might be involved in the impaired growth and metastatic ability mediated by DYNC1H1 loss in NSCLC. DYNC1H1 might serve as a promising biological marker of prognosis and a potential clinical therapeutic target for patients with NSCLC.


Suppression of alcohol consumption in C57Bl/6 mice after intranasal administration of antiserotonin antibodies.
Experiments on C57Bl/6 mice under conditions of free choice between alcohol and water for 10 months showed that intranasal administration with antiserotonin antibodies in doses of 30 and 15 microg/kg for 2 week decreased alcohol consumption over 1 month after treatment.


Use of dopamine agonist pergolide in outpatient treatment of cocaine dependence.
The dopamine agonist pergolide was evaluated in the treatment of 42 men who manifested cocaine dependence in a single-blind, 4-week-long placebo-controlled study, during 1998-1999 in São Paulo, Brazil. The patients were randomly assigned to two groups: the first group received pergolide (0.05-0.2 mg per day) and the second group received placebo (one to four tablets per day). Urine toxicology screens were obtained. The groups were compared in terms of depressive symptoms, "craving," use of cocaine, side effects of medications, results of urine tests, and retention in treatment. At 3 months' follow-up, the participants were reassessed. No differences were found between the two groups.


Imaged guided surgery during arteriovenous malformation of gastrointestinal stromal tumor using hyperspectral and indocyanine green visualization techniques: A case report.
This case report demonstrates the simultaneous development of a gastrointestinal stromal tumour (GIST) with arteriovenous malformations (AVMs) within the jejunal mesentery. A 74-year-old male presented to the department of surgery at our institution with a one-month history of abdominal pain. Contrast-enhanced computed tomography revealed an AVM. During exploratory laparotomy, hyperspectral imaging (HSI) and indocyanine green (ICG) fluorescence were used to evaluate the extent of the tumour and determine the resection margins. Intraoperative imaging confirmed AVM, while histopathological evaluation showed an epithelioid, partially spindle cell GIST. This is the first case reporting the use of HSI and ICG to image GIST intermingled with an AVM. The resection margins were planned using intraoperative analysis of additional optical data. Image-guided surgery enhances the clinician's knowledge of tissue composition and facilitates tissue differentiation. Since image-guided surgery is safe, this procedure should increase in popularity among the next generation of surgeons as it is associated with better postoperative outcomes.


Open learning. Support for the learner-led team.
Employing open learning in educational programmes relies for its success on a firm integral structure. Patsy Poppleton argues that clearly defined roles with adequate support for all participants is essential.


Effect of potassium on nitrate removal from groundwater in agricultural waste-based heterotrophic denitrification system.
Heterotrophic denitrification based on solid carbon sources has been widely investigated for nitrogen removal in recent years. In this study, the response of the heterotrophic denitrification process under different K+ concentrations was clarified. Additionally, the denitrification enhancement mechanism was revealed and resource utilization of agricultural waste was achieved. A series of batch tests were conducted to study the effect of different K+ concentrations on the denitrification performance, dissolved organic matter (DOM) dissolution and microbial community structure. Results demonstrate that the threshold of K+ concentration for the NO3--N and NO2--N reduction rates were 229.78 ± 25.80 and 159.10 ± 24.60 mg-K/L, respectively. Excitation-emission matrix (EEM) analysis identified the main DOM components associated with tyrosine-like, tryptophan-like and humic-like substances, as well as illustrated the evolutionary behavior and utilization of DOM. High throughput 16S rRNA gene sequencing indicates that a K+ concentration of 229.78 ± 25.80 mg-K/L exhibited the highest diversity of functional species associated with fermentation and denitrification. The genera Pseudomonas and Thiobacillus were the unique denitrifiers at this K+ concentration. The correlation of K+ concentration, DOM dissolution of different regions and microorganism structure were analyzed using correlation matrix and PCA, and the appropriate K+ concentration of different functional microorganisms survival was optimized by this analysis method.


[Alveolo-interstitial pneumonia due to Temozolamide].
Temozolomide is an alkylating agent approved for treatment of glioblastoma in association with radiotherapy. We report the case of a 56 year old woman presenting with alveolo-interstitial pneumonia after treatment with Temozolomide. Initially she received induction treatment with Temozolomide and concomitant radiotherapy for bifocal high grade glioblastoma. A month later she received, as scheduled, the first course of Temozolomide maintenance chemotherapy. Grade II dyspnoea developed a few days later. High resolution computed tomography showed alveolo-interstitial opacities with basal predominance, associated with alveolar nodules. Broncho-alveolar lavage showed a lymphocytosis. No bacteria were isolated from microbiological samples. A final diagnosis of drug-induced pneumonia was based on the time sequence and absence of other causes. There is little literature concerning the pulmonary toxicity of Temozolomide. However, our case report of drug-induced pneumonia and similar observations in the databases of regional pharmacovigilance centres suggest that this side effect should be included in the summary of product characteristics.


Antimicrobial resistance trends in community-acquired respiratory tract pathogens in the Western Pacific Region and South Africa: report from the SENTRY antimicrobial surveillance program, (1998-1999) including an in vitro evaluation of BMS284756.
From 1998 to 1999, a large number of community-acquired respiratory tract isolates of Streptococcus pneumoniae (n=566), Haemophilus influenzae (n=513) and Moraxella catarrhalis (n=228) were collected from 15 centres in Australia, Hong Kong, Japan, China, the Philippines, Singapore, South Africa and Taiwan through the SENTRY Antimicrobial Surveillance Program. Isolates were tested against 26 antimicrobial agents using the NCCLS-recommended methods. Overall, 40% of S. pneumoniae isolates were resistant to penicillin with 18% of strains having high-level resistance (MIC > or =2 mg/l). Rates of erythromycin and clindamycin resistance were 41 and 23%, respectively. Penicillin-resistant strains showed high rates of resistance to other antimicrobial agents: 96% to trimethoprim-sulphamethoxazole (TMP-SMX), 84% to tetracycline and 81% to erythromycin. A significant proportion of penicillin-susceptible strains was also resistant to erythromycin (21%), tetracycline (29%) and TMP-SMZ (26%). Small numbers of strains were resistant to levofloxacin (0.7%), trovafloxacin (0.4%) and grepafloxacin (1.3%) where as all strains remained uniformly susceptible to quinupristin/dalfopristin and BMS284756 (MIC(90), 0.06 mg/l), a new desfluoroquinolone. beta-lactamases were, produced by 20% H. influenzae isolates and only rare strains showed intrinsic resistance to amoxycillin. Other beta-lactam agents showed good activity with rates of resistance less than 2% and all isolates showed susceptibility to cefixime, ceftibuten, cefepime and cefotaxime. Rates of resistance to tetracycline and chloramphenicol were also relatively low at 3%. The majority (98%) of M. catarrhalis isolates was found to be beta-lactamase-positive and resistant to penicillins, however, resistance to erythromycin and tetracycline was also low at 1.8%. Both H. influenzae and M. catarrhalis isolates were uniformly susceptible to the new desfluoroquinolone and tested fluoroquinolones.


Expression QTLs Mapping and Analysis: A Bayesian Perspective.
The aim of expression Quantitative Trait Locus (eQTL) mapping is the identification of DNA sequence variants that explain variation in gene expression. Given the recent yield of trait-associated genetic variants identified by large-scale genome-wide association analyses (GWAS), eQTL mapping has become a useful tool to understand the functional context where these variants operate and eventually narrow down functional gene targets for disease. Despite its extensive application to complex (polygenic) traits and disease, the majority of eQTL studies still rely on univariate data modeling strategies, i.e., testing for association of all transcript-marker pairs. However these "one at-a-time" strategies are (1) unable to control the number of false-positives when an intricate Linkage Disequilibrium structure is present and (2) are often underpowered to detect the full spectrum of trans-acting regulatory effects. Here we present our viewpoint on the most recent advances on eQTL mapping approaches, with a focus on Bayesian methodology. We review the advantages of the Bayesian approach over frequentist methods and provide an empirical example of polygenic eQTL mapping to illustrate the different properties of frequentist and Bayesian methods. Finally, we discuss how multivariate eQTL mapping approaches have distinctive features with respect to detection of polygenic effects, accuracy, and interpretability of the results.


Risk of Stroke in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.
Observational studies, to date, have provided inconsistent findings on whether inflammatory bowel disease (IBD) is associated with an increased risk of stroke. We therefore performed a meta-analysis to evaluate the association of IBD and its specific subtypes with risk of stroke. We searched electronic databases for studies through May 13, 2015 assessing risk of stroke in patients with IBD. Cohort and case-control studies that reported incident cases of stroke in patients with IBD and a non-IBD control population were eligible. We calculated pooled hazard ratios (HRs) with 95% confidence intervals (CIs). A total of 8 articles (126,493 IBD patients and 4748 cases of stroke) were included in this meta-analysis. The presence of IBD revealed a trend toward a modest increase in the risk of stroke incidence (HR = 1.29; 95% CI, 1.16-1.43). After subgroup analysis, Crohn's disease showed an increased risk of stroke incidence (7 studies: HR = 1.32; 95% CI, 1.13-1.56), and a significant association was also identified in ulcerative colitis (6 studies: HR = 1.18; 95% CI, 1.06-1.31). In addition, this risk is higher in women (6 studies: HR = 1.49; 95% CI, 1.24-1.79) than in men (HR = 1.22; 95% CI, 1.12-1.32). In the overall analysis we found considerable heterogeneity. Our results show a positive association between IBD and the risk of stroke.


Lactate dehydrogenase predicting mortality in patients with aneurysmal subarachnoid hemorrhage.
Lactate dehydrogenase (LDH) has been reported to be associated with outcomes after surgery in patients with aneurysmal subarachnoid hemorrhage (aSAH), but it is unclear if this is independent from other biomarkers and across all aSAH treatments. This study aims to assess whether LDH is an independent predictor of mortality in patients with aSAH and test whether the inclusion of LDH in a well-established prediction model can improve discrimination and reclassification. This was a retrospective observational study at a tertiary academic medical center. This study measured baseline LDH levels taken at admission and longitudinal LDH levels (up to a month postadmission) to assess median, max, and trajectory LDH levels. The primary outcome was mortality at 90 days. Multivariable regression analyses were used to evaluate associations between LDH and outcomes. The full original Subarachnoid Hemorrhage International Trialists' (SAHIT) model was used as the reference model. In total, 3524 patients with aSAH were included. LDH at admission was independently associated with mortality at 90 days (quartile 4 vs. 1: odds ratio 1.60; 95% CI 1.08-2.37) and mortality at the longest follow-up (quartile 4 vs. 1: hazard ratio1.72; 95% CI 1.34-2.20). Compared with the SAHIT model, the addition of three LDH (admission, max, and median) levels to the SAHIT model significantly improved the area under the curve and categorical net reclassification improvement for prediction mortality. In patients with aSAH, LDH level is an independent predictor of all-cause mortality. The incorporation of LDH into a well-established prediction model improved the ability to predict the risk of death in patients with aSAH.


Compensatory Hippocampal Recruitment Supports Preserved Episodic Memory in Autism Spectrum Disorder.
The degree to which individuals with autism spectrum disorder (ASD) evidence impairments in episodic memory relative to their typically developing (TD) counterparts remains unclear. According to a prominent view, ASD is associated with deficits in encoding associations between items and recollecting precise context details. Here, we evaluated behavioral and neural evidence for this impaired relational binding hypothesis using a task involving relational encoding and recollection during functional magnetic resonance imaging. Adolescents and young adults (nASD = 47, nTD = 60) performed the Relational and Item-Specific Encoding task during functional magnetic resonance imaging, including item and associative recognition testing. We modeled functional recruitment within the medial temporal lobes (MTLs), and connectivity between MTL and the posterior medial (PM) network thought to underlie relational memory. The impaired relational binding model would predict a behavioral deficit driven by aberrant recruitment and connectivity of MTL and the PM network. The ASD and TD groups showed indistinguishable item and associative recognition performance. During relational encoding, the ASD group demonstrated increased hippocampal recruitment, and decreased connectivity between MTL and PM regions relative to the TD group. Within ASD, hippocampal recruitment and MTL-PM connectivity were inversely correlated. The lack of a behavioral deficit in ASD does not support the impaired relational binding hypothesis. Instead, the current data suggest that increased recruitment of the hippocampus compensates for decreased MTL-PM connectivity to support preserved episodic memory in ASD. These findings suggest a compensatory neurodevelopmental mechanism that may support preserved cognitive domains in ASD: local hyperrecruitment may offset connectivity aberrations in individuals with ASD relative to TD subjects.


Crystallization of a synthetic analog of calcium-binding site III of rabbit skeletal troponin C.
Single crystals of the calcium-binding peptide AcA98STnC (90-123)amide, which is a synthetic fragment analog of rabbit skeletal troponin C calcium-binding site III, have been grown in the tetragonal crystal system. Crystals were developed to a maximum size of 0.60 x 0.60 x 0.75-mm by the technique of washing and reseeding. The space group is I41 with a = 40.21(1) A, c = 34.07(1) A; there is 1 polypeptide fragment/crystallographic asymmetric unit, and the solvent content is estimated to be 29%. The crystals diffract to at least 1.8-A d spacings and are stable in the x-ray beam for 1 week.


Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations.
Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features. The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1. Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (AI) (inherited abnormal dental enamel formation). Mild facial dysmorphism was noted in the absence of other obvious skeletal or growth abnormalities. A mild hypophosphataemia and soft tissue ectopic mineralization were present. A homozygous FAM20C donor splice site mutation (c.784 + 5 g > c) was identified which led to abnormal cDNA sequence. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism. There was hypophosphataemia, soft tissue ectopic mineralization, but no osteosclerosis. A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified. The clinical phenotype of non-lethal Raine Syndrome is more variable, including between affected siblings, than previously described and an adverse impact on bone growth and health may not be a prominent feature. By contrast, a profound failure of dental enamel formation leading to a distinctive hypoplastic AI in all teeth should alert clinicians to the possibility of FAM20C mutations.


Post-transcriptional modulation of interleukin 8 by CNOT6L regulates skeletal muscle differentiation.
CNOT6L is a deadenylase subunit belonging to the CCR4-NOT complex, a major deadenylase complex in eukaryotes involved at multiple levels in regulation of gene expression. While CNOT6L is expressed in skeletal muscle cells, its specific functions in this tissue are still largely unknown. Our previous work highlighted the functional of CNOT6L in skeletal muscle cell differentiation. To further explore how CNOT6L regulates myogenesis, we used here gene expression analysis to identify CNOT6L mRNA targets in human myoblasts. Among these novel targets, IL-8 (interleukin 8) mRNA was the most upregulated in CNOT6L knock-down (KD) cells. Biochemical approaches and poly (A) tail length assays showed that IL-8 mRNA is a direct target of CNOT6L, and further investigations by loss- and gain-of-function assays pointed out that IL-8 is an important effector of myogenesis. Therefore, we have characterized CNOT6L-IL-8 as a new signaling axis that regulates myogenesis.


Increased parahippocampal and lingual gyrification in first-episode schizophrenia.
Cerebral gyrification is attributed to a large extent to genetic and intrauterine/perinatal factors. Hence, investigating gyrification might offer important evidence for disturbed neurodevelopmental mechanisms in schizophrenia. As an extension of recent ROI analyses of gyrification in schizophrenia the present study is the first to compare on a node-by-node basis mean curvature as a sensitive parameter for the identification of local gyrification changes of the whole cortex in first-episode schizophrenia. A group of 54 patients with first-episode schizophrenia according to DSM-IV and 54 age and gender matched healthy control subjects were included. All participants underwent high-resolution T1-weighted MRI scans on a 1.5 T scanner. Mean curvature was calculated dividing the sum of the principal curvatures by two at each point of the curved surface as implemented in the Freesurfer Software package. Statistical cortical maps were created to estimate gyrification differences between groups based on a clustering approach. A significantly increased gyrification was observed in first-episode schizophrenia patients relative to controls in a right parahippocampal-lingual cortex area. The cluster encompassed a surface area of 750 mm². A further analysis of cortical thickness of this cluster demonstrated concurrent significant reduced cortical thickness of this area. This is the first study to reveal an aberrant gyrification of the medial surface in first-episode schizophrenia. This finding is in line with substantial evidence showing medial temporal lobe abnormalities in schizophrenia. The present morphometric data provide further support for an early disruption of cortical maturation in schizophrenia.


Late metabolic acidosis: a reassessment of the definition.
The term "late metabolic acidosis" is generally used to define a population of apparently healthy LBW infants who fail to grow and have a base deficit in excess of 5 mEq/l (CO2TOT less than 21 mM). A relationship between hypobasemia and the lack of appropriate growth was postulated. This conclusion was reached, however, in the absence of adequate information regarding the distribution of acid-base variables in healthy LBW infants. The results of this study demonstrate that the CO2TOT of LBW infants (n = 114) rises between birth and three weeks of life from a mean of 18.6 to 20.3 mM. The frequency distribution of CO2TOT values did not show any significant deviations from normality, and 2 SD included values as low as 14.5 mM. No difference in the rate of growth was detected between "hypobasemic" infants given a solution of bicarbonate calculated to bring their blood CO2TOT to greater than 21 mM and those given similar amounts of isotonic saline solution. The ability of the LBW infants to excrete an ammonium chloride load was not related to their acid-base status and was comparable to that of term infants. It is apparent that the definition of late metabolic acidosis needs to be reconsidered.


OCT En Face Analysis of the Posterior Vitreous Reveals Topographic Relationships among Premacular Bursa, Prevascular Fissures, and Cisterns.
To characterize the topographic relationships among vitreous structures, including the premacular bursa, prevascular vitreous fissures, cisterns, and lacunae, in healthy participants using en face and cross-sectional swept-source (SS) OCT. Prospective, comparative study. Sixty eyes of 60 healthy participants (age range, 4-35 years). Eyes of individuals younger than 20 years (n = 29) were compared with eyes of individuals 20 years of age or older (n = 31). From each study eye, 12 × 12-mm SS OCT volume scans comprising 1024 × 1024 A-scans centered at the fovea were acquired. En face and cross-sectional data were analyzed to characterize topographic relationships between hyperreflective spaces anterior to the vitreoretinal interface. Prevascular vitreous fissures are an almost universal feature of human eyes. Cisterns became more prevalent over the course of the first 20 years (r = 0.49; P = 0.002). In 97% of eyes in individuals older than 20 years, en face and cross-sectional SS OCT showed the premacular bursa and prepapillary gap merge at a distance superior to the optic nerve and then follow a superonasal course anteriorly. However, only 69% of individuals younger than 20 years demonstrated such a connection (P = 0.01). A close topographic relationship of vitreous fissures and cisterns to the underlying vasculature of the posterior pole was visible on en face projections. En face imaging readily distinguished these spaces. Degenerative, eyewall-parallel fissure planes and their course were described for the first time in a 3-dimensional manner. The fissure planes were rare in younger eyes (12%) and significantly more common in older eyes (42%; P < 0.001). En face SS OCT demonstrated that (1) premacular bursa and Cloquet's canal are not connected in younger patients, but are connected in older patients; (2) prevascular vitreous fissures overly the retinal vessels; and (3) cisterns are continuous with prevascular fissures.


Bleomycin-induced chromosomal aberrations in Down's syndrome lymphocytes.
Blood samples from 4 Down's syndrome (DS) patients with a 47,XY,21 + karyotype and from 4 normal male probands were cultured for 72 h in the presence of BrdU and lymphocytes analysed at their first mitosis for chromosomal aberrations. The frequencies of spontaneous aberrations and the proportions of cells in the first or later mitoses in culture were not different between the groups. Treatment with various doses of bleomycin in vitro resulted in similar delays in cell development for both DS and normal lymphocytes and dose-dependent increases in the incidence of chromosome-type aberrations. However, the induction of both dicentric aberrations and acentric fragments was significantly enhanced in DS cells relative to cells of normal karyotype.


Brain metastases from ovarian cancer.
Brain metastasis from ovarian carcinoma is a relatively rare phenomenon. At NYU Medical Center five patients were treated for this entity from 1982 to 1985. The stage at presentation ranged from stage I to stage III, and all patients had received or were receiving chemotherapy. Two patients had active disease elsewhere at diagnosis of brain metastasis, but three patients were otherwise NED. Three patients had solitary cerebellar disease, and two patients had multiple lesions. All patients were treated with whole brain radiotherapy to 3,000 cGy, with neurological improvement in three of the five patients. The central nervous system may need special consideration for prophylactic treatment in those patients with ovarian cancer who receive adjuvant chemotherapy.


Reaction of glutathione with conjugated carbonyls.
1. GSH reacts with conjugated carbonyls according to the equation: GSH+R-CH=CH-COR in equilibrium R-CH(SG)-CH2-COR. The forward reaction follows second order, the reverse reaction first order kinetics. It is assumed that this reaction reflects best the ability of conjugated carbonyls to inactivate SH groups in biological systems. 2. The rate of forward reaction increases with pH approx. parallel with alphaSH. Besides OH- ions also proton donors (e.g. buffers) increase the rate. The catalytic effect of pH and buffer is interpreted in view of the reaction mechanism. 3. The equilibrium constants as well as the rate constants for forward (k1) and reverse reaction show an extreme variation depending on the carbonyl structure. Acrolein and methyl vinyl ketone (k1 = 120 and 32 mol-1 sec-1, resp.) react more rapidly than any other carbonyl to give very stable adducts (half-lives for reverse reaction 4.6 and 60.7 days, resp). Somewhat less reactive are 4-hydroxy-2-alkenals and 4-ketopentenoic acid (k1 between 1 and 3 mol-1 sec-1), but they also form very stable adducts showing half-lives between 3.4 and 19 days. All other carbonyl studied react either very slowly (e.g. citral, ethly crotonate, mesityl oxide, acrylic acid) or form very labile adducts (crotonal, pentenal, hexenal, 3-methyl-butenone). Comparing biological activities of conjugated carbonyls their reactivity towards HS (k1) and the stability of the adducts must be considered.


Non-Hodgkin's malignant lymphomas in patients older than 80. 70 cases.
In two centers (a comprehensive cancer center and a university hospital) 1300 patients with non-Hodgkin's lymphomas (NHL) were observed during the past 15 years. Seventy patients (5.4%) were diagnosed after they were 80 years old. Thirty-four patients had low-grade NHL, eight had intermediate grade, and 28 had high-grade NHL. The majority of them were classified as Stage I (n = 24) or II (n = 18), and the rest as Stage III (n = 16) or IV (n = 12). Treatment varied with grade of NHL, tumoral extension, and performance status. Forty-seven patients were given chemotherapy, 37 radiotherapy, and six patients had surgery. Overall, treatment was considered to be optimal in 12 patients, good in 34 patients, and limited in 24 patients. Toxicity was minimal in 62 patients, treatment-limiting in two patients, and lethal in six patients. Thirty-seven patients achieved a complete remission (CR), 21 a partial remission, five experienced stabilization, and seven failed to respond. For all patients, the median survival (MS) was 18 months. In contrast to younger patients, malignancy grade had no significant influence. The only significant parameter is CR (P = 0.02). In conclusion, very old patients must be treated correctly but carefully. Better tolerated treatments are needed to improve results that are neither very poor nor as good as in younger patients.