Prediction of mutation effects using a deep temporal convolutional network.
Accurate prediction of the effects of genetic variation is a major goal in biological research. Towards this goal, numerous machine learning models have been developed to learn information from evolutionary sequence data. The most effective method so far is a deep generative model based on the variational autoencoder (VAE) that models the distributions using a latent variable. In this study, we propose a deep autoregressive generative model named mutationTCN, which employs dilated causal convolutions and attention mechanism for the modeling of inter-residue correlations in a biological sequence. We show that this model is competitive with the VAE model when tested against a set of 42 high-throughput mutation scan experiments, with the mean improvement in Spearman rank correlation ∼0.023. In particular, our model can more efficiently capture information from multiple sequence alignments with lower effective number of sequences, such as in viral sequence families, compared with the latent variable model. Also, we extend this architecture to a semi-supervised learning framework, which shows high prediction accuracy. We show that our model enables a direct optimization of the data likelihood and allows for a simple and stable training process. Source code is available at https://github.com/ha01994/mutationTCN. Supplementary data are available at Bioinformatics online.


Mutational landscape of SWI/SNF complex genes reveal correlation to predictive biomarkers for immunotherapy sensitivity in lung adenocarcinoma patients.
The search for prognostic biomarkers indicating sensitivity to immunotherapy in lung adenocarcinoma patients has zeroed in on genes in the switch/sucrose non-fermentable (SWI/SNF) pathway. The mutational profiles of key genes are not clearly defined, however, and no comparisons have been conducted on whether mutations in the genes involved provide the same predictive value. In this study, analysis of clinical factors, tumor mutation burden (TMB), chromosomal instability, and co-alterations was conducted for 4344 lung adenocarcinoma samples. Independent online cohorts (N = 1661 and 576) were used to supplement the analysis with survival and RNA-seq data. Mutational burden and chromosomal instability analysis showed that ARID family mutations (including ARID1A, ARID1B, or ARID2 mutations) and SMARC family mutations (including SMARCA4 or SMARCB1 mutations) display different profiles from wild-type (WT) samples (TMB: ARID versus WT: P < 2.2 × 10-16, SMARC versus WT: P < 2.2 × 10-16; CIN: ARID versus WT: P = 1.8 × 10-5, SMARC versus WT: P = 0.027). Both mutant groups have a higher proportion of transversions than transitions, whereas the ratio is more equal for wild-type samples. Survival analysis shows that patients with ARID mutations were more sensitive to immunotherapy treatment than wild-type and SMARC-mutated patients (P < 0.001 and P = 0.013, respectively), and multivariate Cox analysis reveals that the presence of ARID mutations is likely the main cause. The research presented in this study shows that mutations in the ARID gene family, including ARID1A, ARID1B, and ARID2, are primarily responsible for the sensitive response to immunotherapy treatment in patients with lung adenocarcinoma.


The ontogeny of efficient second-order action planning: The developing interplay of controlled and habitual processes in goal-directed actions.
The ability to act efficiently plays an important role in everyday human life. The current study investigated efficient motor planning in 2- to 14-year-old children and adults (N = 246) in two different object manipulation tasks that involved everyday objects (a cup and a spoon). Importantly, we manipulated whether or not the efficient controlled grasp was incongruent with the habitual use of the object. We assessed to what extent participants planned their grasping action in an anticipatory controlled manner or relied on the habitual use of an object. We found the ability of efficient movement planning to be correlated between the two conceptually different tasks. Furthermore, the interplay of controlled and habitual processes of action control showed different developmental patterns for the two tasks and does not indicate a simple linear developmental trend. Thus, this study expands our knowledge on the ontogeny of efficient motor planning and highlights the developmental dynamics of the interplay of controlled and habitual processes in goal-directed action control.


Thumb reconstruction by free transplantation of a damaged index ray from the other hand: case report.
We feel that the success rate of microvascular anastomosis, for surgeons experienced in it, provides, in selected cases, a method for thumb reconstruction which satisfies most or all of the desired goals. It also provides a means for preserving damaged parts--ones of limited value--and getting more important functions from them.


Cerebrospinal fluid lactate level in aquaporin-4 antibody positive neuromyelitis optica spectrum disorders: a hint on differential diagnosis and possible immunopathogenesis.
Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) may be similar to each other in clinical features. The differential diagnosis between them remains challenging in clinical practice. This retrospective study is aimed to describe the difference of cerebrospinal fluid (CSF) lactate level between aquaporin-4 antibody (AQP4-Ab) positive NMOSD and MS, to discuss the possible explanation upon immunopathogenesis and the significance in differential diagnosis. We retrospectively analysed cerebral biochemical results from 60 AQP4-Ab positive NMOSD and 55 MS Asian patients. To assess the diagnostic ability of cerebrospinal fluid lactate for distinguishing AQP4-Ab positive NMOSD from MS using receiver operating characteristic (ROC) curve analysis. The cerebrospinal fluid lactate level is significantly higher in AQP4-Ab positive NMOSD than in MS based on multiple linear regression (P<0.0001). The differential diagnostic efficacy of cerebrospinal fluid lactate distinguishing AQP4-Ab positive NMOSD from MS reached an area under ROC curve (AUC) of 0.8842 (95% CI 0.82-0.95, P<0.0001), using 1.50 as the diagnostic critical point of the cerebrospinal fluid lactate level, the sensitivity was 88.3%, the specificity was 78.2%. The cerebrospinal fluid lactate level differs between AQP4-Ab positive NMOSD and MS, which also contributes in differential diagnosis. The distinct patterns of cerebral biochemical results may cast a light on the immunopathogenesis of AQP4-Ab positive NMOSD.


Vascular effects of the peptides PYY and PHI: comparison with APP and VIP.
Local infusions of PYY (3-100 pmol.min-1) caused a slowly developing vasoconstriction of a long duration in the cat submandibular salivary gland. The vasoconstrictor action of PYY was also present after alpha-adrenoceptor blockade and in sympathectomized animals. Local APP infusions caused only weak vasoconstriction. Infusions of PHI and synthetic PHI caused an atropine-resistant submandibular vasodilation. On a molar basis PHI was, however, almost 1000-fold less potent than VIP as vasodilating agent.


Effectiveness of right or left radial approach for coronary angiography.
The transradial approach for catheterization is becoming increasingly more popular. At present, the choice of the right or left radial artery depends on the operator's preference. We examined how the laterality influenced the effectiveness of the approach. Employing Judkins-type catheters, we performed coronary angiography in 232 patients with the left approach and in 205 patients with the right approach. Although access time did not differ between the two groups of patients, the duration of catheter manipulation was shorter in the left- than in the right-approach group (11.7 +/- 5.9 vs. 9.8 +/- 4.4 min; P < 0.001). Because of the shorter duration of catheter manipulation, the total procedural duration was shorter in the left-approach group (13.7 +/- 6.4 vs. 11.4 +/- 4.8 min; P < 0.001). The fluoroscopy time was shorter in the left- than in the right-approach group (3.7 +/- 2.5 vs. 5.0 +/- 3.3 min; P < 0.001). The amount of contrast material did not differ between the groups (79 +/- 27 vs. 83 +/- 25 ml). The rate of guidewire usage to engage the coronary ostium was higher in the right- than in the left-approach group because of the severe tortuosity of the right subclavian artery (20/205 vs. 0/232; P < 0.001). Thus, for operators with significant experience, the left radial approach may provide increased procedural efficacy for coronary angiography compared to the right radial approach.


Machine learning prediction of nitrogen heterocycles in bio-oil produced from hydrothermal liquefaction of biomass.
Hydrothermal liquefaction (HTL) of high-moisture biomass or biowaste to produce bio-oil is a promising technology. However, nitrogen-heterocycles (NH) presence in bio-oil is a bottleneck to the upgrading and utilization of bio-oil. The present study applied the machine learning (ML) method (random forest) to predict and help control the bio-oil NH, bio-oil yield, and N content of bio-oil (N_oil). The results indicated that the predictive performance of the yield and N_oil were better than previous studies, achieving test R2 of 0.92 and 0.95, respectively. Acceptable predictive performance (test R2 of 0.82 and RMSE of 7.60) for the prediction of NH was also achieved. The feature importance analysis, partial dependence, and Shapely value were used to interpret the prediction models and study the NH formation mechanisms and behavior. Then, forward optimization of NH was implemented based on optimal predictive models, indicating the high potential of ML-aided bio-oil production and engineering.


Comparative Evaluation of Myeloperoxidase Enzymatic Activity in Gingival Crevicular Fluid of Subjects having Orthodontic Treatment by Different Aligning Arch Wires.
There exist a number of factors that affect the outcome of orthodontic treatment. These factors can be assessed by various gingival markers. One such maker is myeloperoxidase (MPO). Hence, we planned the present study to assess and compare the MPO activity in the gingival crevicular fluid (GCF) of subjects undergoing orthodontic treatment by different aligning arch wires. The present study included assessment of patients who underwent orthodontic treatment for crowding of anterior teeth. Diagnostic cast models of all the subjects were made for recording the irregularity index. All the subjects were randomly divided into three study groups with 15 patients in each group based on the type of nickel-titanium (NiTi) arch wires used. A collection of GCF samples was done in all the patients at various time intervals and it was sent to the laboratory for assessment of MPO activity. Activity of the MPO enzyme was expressed in terms of number of units per 100 μL. All the results obtained were compiled and analyzed by Statistical Package for the Social Sciences (SPSS) software. We observed that nonsignificant results were obtained while comparing the mean age and mean gingival score in all the study groups. However, significant results were obtained on comparing the mean MPO enzymatic activity in all the study groups at different time intervals. Both superelastic NiTi and heat-activated NiTi generate optimal forces, which are necessary for higher metabolic response of the periodontal ligament. In the intimal stages of orthodontic treatment, both superelastic NiTi and heat-activated NiTi wires are superior in leveling and aligning the crowded teeth.


Association Between Behavioral, Biological, and Genetic Markers of Cardiovascular Health and MRI Markers of Brain Aging: A Cohort Study.
The life's simple 7 approach was proposed to define cardiovascular health (CVH) metrics. We sought to investigate the associations between behavioral, biological, and genetic markers for CVH and vascular brain aging in older adults. This population-based cohort study included participants who had repeated brain MRI measures from 2001 to 2003 to 2007-2010 (i.e., count of perivascular spaces, volumes of white matter hyperintensity [WMH] and gray matter, and lacunes). At baseline, global, behavioral, and biological CVH metrics were defined and scored following the life's simple 7 approach and categorized into unfavorable, intermediate, and favorable profiles according to tertiles. The metabolic genetic risk score was calculated by counting 15 risk alleles associated with hypertension, diabetes, or dyslipidemia. Data were analyzed using linear mixed-effects and Cox proportional hazards models, adjusting for age, sex, and education. The study sample consisted of 317 participants (age 60 years or older; 61.8% women). Favorable and intermediate (vs unfavorable) global CVH profiles were related to slower WMH progression, with β-coefficients (95% CI) being -0.019(-0.035-0.002) and -0.018(-0.034-0.001), respectively. Favorable and intermediate (vs unfavorable) biological CVH profiles were significantly related to slower WMH increase only in people aged 60-72 years. CVH profiles were not related to progression of other brain measures. Furthermore, a higher metabolic genetic risk score (range: 6-21) was associated with faster WMH increase (β-coefficient = 0.005; 95% CI: 0.003-0.008). There were statistical interactions of metabolic genetic risk score with global and behavioral CVH profiles on WMH accumulation. A higher metabolic genetic risk score was related to faster WMH accumulation, with β-coefficients being 0.015(0.007-0.023), 0.005(0.001-0.009), and 0.003(-0.001 to 0.006) among people with unfavorable, intermediate, and favorable global CVH profiles, respectively; the corresponding β-coefficients were 0.013(0.006-0.020), 0.006(0.003-0.009), and 0.002(-0.002 to 0.006) among people with unfavorable, intermediate, and favorable behavioral CVH profiles. Intermediate to favorable global CVH profiles in older adults are associated with slower vascular brain aging. The association of metabolic genetic risk load with accelerated vascular brain aging was evident among people with unfavorable to intermediate, but not favorable, CVH profiles. These findings highlight the importance of adhering to favorable CVH profiles, especially healthy behaviors, in vascular brain health.


Messenger RNA extracted from Schistosoma mansoni larval forms codes for parasite antigens when translated in vitro.
Intact messenger RNA was extracted from three stages of development of the parasite Schistosoma mansoni, cercariae, 3 h (mechanically prepared) schistosomula and adults. Some of the in vitro translation products are precipitable with immune rat and human serum showing that these sera recognize protein determinants. Whereas the patterns of the total translation products show major proteins expressed at all three developmental stages, immunoprecipitation delineates patterns unique to each stage. Serum from chronically infected patients is likely to preferentially recognize proteins expressed by the adult parasite yet precipitates more products of translation of cercarial RNA than of adult RNA, suggesting that many of the same epitopes are already coded by cercarial messenger RNA. It seems, however, that antigens appear on lower molecular weight species in the adult. The experiments described here open the way to cloning the genes of antigens from S. mansoni.


Factors associated with low-dose CT lung cancer screening participation in a high burden state: Results from the 2017-2018 BRFSS.
The purpose of this study was to examine low-dose computed tomography (LDCT) for lung cancer screening (LCS) eligibility, utilization, and factors associated with self-reported participation among eligible individuals. Data from the 2017 and 2018 Oklahoma Behavioral Risk Factor Surveillance System (BRFSS) were used and analysis was restricted to data from individuals eligible for screening based on the US Preventive Services Task Force (USPSTF) guidelines. Analyses using recursive partitioning and weighted logistic regression were conducted from November 2019 to March 2020. The final study sample consisted of 596 respondents. Only 10.84 % of participants reported LCS participation. Differences in participation by sex were observed. Among males, those with COPD were more likely to report participating in screening. Among females, those who self-reported their health status as "fair or worse" were more likely to participate in LCS. Rates of utilization were higher in this study than in earlier estimates; however, utilization of LCS remains suboptimal. Although LCS participation rates were similar for males and females, differences were observed by sex. Opportunities exist to increase screening participation among eligible individuals, and findings from this study can be used for program planning such as patient engagement resources and effective clinical decision support. This study further demonstrates the complex nature of cancer screening participation, specifically LDCT LCS. Under the current USPSTF guidelines only a small proportion of the population is considered eligible thus to prevent lung cancer mortality, the eligibility criteria regarding smoking history and screening age may need to be reevaluated. Furthermore, this study adds to the evidence that strategies to increase screening participation among eligible individuals may need to differ by sex.


The uterine sandwich method for placenta previa accreta in mullerian anomaly: combining the B-lynch compression suture and an intrauterine gauze tampon.
Mullerian duct anomalies may cause obstetric complications, such as postpartum hemorrhage (PPH) and placental adhesion anomalies. Uterine compression suture may be useful for controlling PPH (especially atony). In recent studies, uterine compression sutures have been used in placenta accreta. We report a case of PPH, a placenta accreta accompanying a large septae, treated with B-Lynch suture and intrauterine gauze tampon.


Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration.
Electrospun tubular scaffolds (4 mm inner diameter) based on bio-artificial blends of polyglyconate (Maxon) and proteins such as gelatin and elastin having a spatially designed multilayer structure were prepared for use as vascular tissue scaffolds. Scanning electron microscopy analysis of scaffolds showed a random nanofibrous morphology with fiber diameter in the range of 200-400 nm for protein-blended Maxon, which mimics the nanoscale dimensions of collagen (50-500 nm). The scaffolds have a well interconnected pore structure and porosity up to 82%, with protein blending and multi-layering in contrast to electrospun Maxon scaffolds (67%). Fourier-transform infrared spectroscopy, x-ray diffraction and differential scanning calorimetry results confirmed the blended composition and crystallinity of fibers. Uniaxial tensile testing revealed a strength of 14.46 +/- 0.42 MPa and a modulus of 15.44 +/- 2.53 MPa with a failure strain of 322.5 +/- 10% for a pure Maxon scaffold. The blending of polyglyconate with biopolymers decreased the tensile properties in general, with an exception of the tensile modulus (48.38 +/- 2 MPa) of gelatin/Maxon mesh, which was higher than that of the pure Maxon scaffold. Trilayered tubular scaffolds of gelatin/elastin, gelatin/elastin/Maxon and gelatin/Maxon (GE-GEM-GM) that mimic the complex trilayer matrix structure of natural artery have been prepared by sequential electrospinning. Tensile testing under dry conditions revealed a tensile strength of 2.71 +/- 0.2 MPa and a modulus of 20.4 +/- 3 MPa with a failure strain of 140 +/- 10%. However, GE-GEM-GM scaffolds tested under wet conditions after soaking in a phosphate buffered saline medium at 37 degrees C for 24 h exhibited mechanical properties (2.5 MPa tensile strength and 9 MPa tensile modulus) comparable to those of native femoral artery.


Separation of some polypeptide hormones by high-performance liquid chromatography.
Twenty-one analogues of ACTH, three analogues of LH-RH and four insulins have been successfully separated on a commercial reversed-phase material with tartrate buffer--acetonitrile systems containing sodium 1-butanesulphonate and sodium sulphate as the mobile phase. The effect of the constituent amino acid residues on the order of elution has been studied in detail by using a variety of closely related peptides; the order of elution of a series of peptides, which differ by only one amino acid residue, can in most instances be explained in terms of the difference in the hydrophobicities of the amino acid residues concerned, but in some instances, such as in diastereoisomers or positional isomers, the order of elution must be interpreted in terms of the hydrophobicity of the whole peptide molecule. This chromatographic method has been proved to be very useful for the rapid examination of the purity of these peptide hormones and for the separation of closely related peptides with molecular weights up to ca. 6000.


Structure of the steroid-binding site of human placental estradiol-17beta-dehydrogenase.
We recently demonstrated that human placental estradiol-17beta-dehydrogenase possesses a histidyl residue in the catalytic region of the active site by affinity-labeling studies with 16alpha-bromoacetoxyestradiol-3-methyl ether. We now report the synthesis of 12beta-bromoacetoxy-4-estrene-3,17-dione and its use in affinity labeling of the enzyme. The steroid was synthesized by incubation of 4-estrene-3,17-dione with Colletotrichum gloesporioides. The product was recrystallized from ethanol and structure assured by IR and NMR spectroscopy. The steroid is a substrate, which indicates that it binds at the active site. When the enzyme is incubated with a 150-fold molar excess of 12beta-bromoacetoxy-4-estrene-3,17-dione in potassium phosphate buffer at pH 7.0, the enzyme is inactivated in a time-dependent, irreversible manner. Inactivation follows pseudo-first-order kinetics with a half life of 18 hours. Analysis of a hydrolysate of the enzyme after inactivation with 12beta-bromo[2'-3H]acetoxy-4-estrene-3,17-dione reveals tritiated 1-, 3-, and 1,3-dicarboxymethylhistidine. The affinity labeling of a histidyl enzyme residue by both 16alpha- and 12beta-bromoacetoxy steroids localizes that residue near the point of catalysis and suggests that it may participate in the catalytic event.


Amidinyl Radical Formation through Anodic N-H Bond Cleavage and Its Application in Aromatic C-H Bond Functionalization.
We report herein an atom-economical and sustainable approach to access amidinyl radical intermediates through the anodic cleavage of N-H bonds. The resulting nitrogen-centered radicals undergo cyclizations with (hetero)arenes, followed by rearomatization, to afford functionalized tetracyclic benzimidazoles in a highly straightforward and efficient manner. This metal- and reagent-free C-H/N-H cross-coupling reaction exhibits a broad substrate scope and proceeds with high chemoselectivity.


ACTH self-administration in rats.
The ability of rats to learn a lever pressing response reinforced by a contingent intravenous delivery of ACTH 1--24 and 4--10, was investigated. About 60% of the rats tested learned to press the lever for the two analogues that were infused at a rate of 2.08 microgram per second via a chronically implanted intrajugular catheter. Most of the animals exhibited sustained daily self-injections of 250 to 375 microgram of ACTH 1--24 and more variable amounts of ACTH 4--10. Comparisons with the self-administration of saline and altered responses following a change in the concentration of ACTH 1--24 solution indicated a positively reinforcing effect for the neuropeptide. The self-administration of the ACTH 4--10 analogue demonstrates that this reinforcing property of ACTH is not due to its adrenal stimulating activity. Brain targets possibly involved in the self-administration of ACTH are discussed.


Family Economics and Mental Health Among High-School Students During COVID-19.
The COVID-19 pandemic has had unprecedented socioeconomic and health impacts in the U.S. This study examined racial/ethnic and school poverty status differences in the relationship between parent job loss, experiences with hunger, and indicators of mental health problems among public high-school students nationwide during the COVID-19 pandemic. The study analyzed data from the Adolescent Behaviors and Experiences Survey, conducted in January-June 2021. The Adolescent Behaviors and Experiences Survey was a 1-time, cross-sectional, online survey that used a stratified, 3-stage cluster sample to obtain a nationally representative sample of high-school students in the U.S. This study was limited to public-school students (n=7,379). Among public high-school students nationwide, 36.9% experienced poor mental health during the pandemic, and during the past year, 43.9% experienced persistent feelings of sadness or hopelessness, 19.8% seriously considered attempting suicide, and 9.1% attempted suicide. Parent job loss and having gone hungry were associated with indicators of mental health problems overall and across racial/ethnic groups and school poverty status levels. Students who experience parent job loss and hunger are likely to also experience poor mental health and may be at higher risk for suicide.


Gene therapy by proteasome activator, PA28γ, improves motor coordination and proteasome function in Huntington's disease YAC128 mice.
Huntington's disease (HD) is neurologically characterized by involuntary movements, associated with degeneration of the medium-sized spiny neurons (MSNs) and ubiquitin-positive neuronal intranuclear inclusions (NIIs). It has been reported that the proteolytic activities of the ubiquitin-proteasome system (UPS) are generally inhibited in HD patient's brain. We previously discovered that a proteasome activator (PA), PA28γ enhances proteasome activities and cell survival in in vitro HD model. In this study, we aimed to find whether PA28γ gene transfer improves the proteasome activities and pathological symptoms in in vivo HD model. We stereotaxically injected lenti-PA28γ virus into the striatum of mutant (MT) YAC128 HD mice and littermate (LM) controls at 14-18months of age, and validated their behavioral and biochemical changes at 12weeks after the injection. YAC128 mice showed a significant increase in their peptidyl-glutamyl preferring hydrolytic (PGPH) proteasome activity and the mRNA or protein levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF after lenti-PA28γ injection. The number of ubiquitin-positive inclusion bodies was reduced in the striatum of YAC128 mice after lenti-PA28γ injection. YAC128 mice showed significant improvement of latency to fall on the rota-rod test after lenti-PA28γ injection. These data demonstrate that the gene therapy with PA, PA28γ can improve UPS function as well as behavioral abnormalities in HD model mice.


Systematic review and meta-analysis of the efficacy of hilotherapy following oral and maxillofacial surgery.
Craniofacial surgery causes immediate postoperative pain, oedema, and functional limitations. Hilotherapy delivers cooled water to the face at 15°C and may reduce the postoperative recovery time. This work presents a meta-analysis of short-term postoperative outcomes after hilotherapy. Following a systematic literature search, comparative trials of patients undergoing surgical interventions in the maxillofacial region and receiving either hilotherapy or ice-cooling therapy were included for meta-analysis. Demographics and surgical outcomes were extracted. Data were analysed using Comprehensive Meta-Analysis software. Mean (SEM) data were calculated for demographic variables and standardized mean differences with the 95% confidence interval for surgical outcomes. Five trials were analysed, providing 206 patients for evaluation; mean patient age was 29.4 (9.4) years. Hilotherapy reduced pain (10-point visual analogue scale) at 48 h (P<0.010) and 72 h (P<0.050), as well as postoperative facial oedema (P<0.010), compared to ice-cooling treatment. Trismus and facial neurological scores were also improved (P=0.08). Patients preferred hilotherapy to other cooling methods (P<0.010). Hilotherapy appears to be effective in reducing postoperative facial pain, oedema, and trismus, and in improving patient-reported outcomes. Well-designed randomized controlled clinical trials are required to clarify the procedure-specific efficacy of postoperative hilotherapy and optimal durations of treatment.


Management of Traumatic Radial and Ulnar Artery Injuries and Risk Factors for Amputation.
Traumatic injuries to the radial and/or ulnar arteries represent a subset of arterial injuries. In the absence of injury to both forearm arteries, treatment was historically ligation if perfusion was maintained to the hand via the uninjured vessels or adequate collateral vessels. We sought to determine management of traumatic forearm arterial injuries in 2019 and to identify risk factors for major upper extremity amputation. The American College of Surgeons Trauma Quality Improvement Program database was queried by International Classification of Diseases 10 code for patients with traumatic radial and/or ulnar artery injuries within the year 2019. Patient demographics, Injury Severity Score, time to operating room, type of repair, outcomes, and mortality were collected. Multivariable logistic regression was used to identify risk factors for major upper extremity amputation. A total of 4048 patients with traumatic radial and/or ulnar artery injuries were identified. A total of 1907 radial artery operations were performed including repair (59%), ligation (29%), and interposition bypass (12%). A total of 1637 ulnar artery operations were completed including repair (67%), ligation (21%), and interposition bypass (12%). Major upper extremity amputation occurred in 0.6%. Older age (adjusted odds ratio [AOR]: 1.014, 95% confidence interval [CI]: 1.004-1.024, P = 0.0048), blunt mechanism (AOR: 2.457, 95% CI: 1.730-3.497, P < 0.0.0001), and ipsilateral radial and ulnar artery injury (AOR: 2.148, 95% CI: 1.298-3.553, P = 0.0029) were associated with major amputation. Surgical revascularization, time to operating room, fasciotomy, and compartment syndrome were not associated with major amputation, but this may be secondary to Type II error. In the operating room, radial and ulnar artery injuries were managed more often with restoration of flow versus ligation. Older age, blunt mechanism, and ipsilateral radial and ulnar artery injury were associated with major amputation. Amputation rate was low at 3% overall and 0.6% for amputation of the hand or a more proximal level. Upper extremity fracture, upper extremity nerve injury, and ipsilateral radial and ulnar artery injury were associated with need for revision operation.


[Frailty criteria in the elderly: a pilot study].
To measure the frailty of people 75 years or over and who live in their own homes based on Fried's criteria and modified by Ávila-Funes. Pilot study of cross-sectional design. SITE: Primary Health Care Centres (7) in the city of Lleida. A probabilistic sample was selected for every stratum. The total sample was 323 individuals. Socio-demographic characteristics, measurement of the five frailty criteria (involuntary lose of weight, low energy or exhaustion, slow mobility, muscle weakness, low physical activity), and geriatric assessment scales (Charlson Index, Pfeiffer's Test, Katz Index, Lawton and Brody Index, MNA Test and CES-D scale). The prevalence of frailty was 8.5%. Factors associated with frailty were, female sex and low monthly income. It was observed that if the frailty increases, there is deterioration of cognitive status, activities of daily living and nutritional status. There is also higher morbidity. Frailty criteria scores showed a significant correlation with geriatric assessment scales scores. The prevalence of frailty in elderly people is similar to those in other studies that have used the same criteria. The measurement of frailty criteria in this study demonstrates a better ability for transcription of results. A frailty study using specific markers enhances prevention and improvement of new intervention programs.


Pelvic Girdle Pain in Pregnancy: A Review.
Pelvic girdle pain is often thought to be a recent phenomenon, but this condition was described as early as 400 BC by Hippocrates. Despite being identified for years, confusion continues about the definition and management of this ailment affecting many pregnancies. The purpose of the review is to assess the incidence, etiology, pathophysiology, risk factors, diagnosis, management, and pregnancy outcomes/recovery of current pregnancies, and outcomes of future pregnancies complicated by pelvic girdle pain. Electronic databases (PubMed and Embase) were searched from 1980 to 2021 with the only limitation being that the articles were in English. Studies were selected that examined associations between pelvic pain/pelvic girdle pain and pregnancy. There were 343 articles identified. After reviewing the abstracts, 88 were used in this review. Pelvic girdle pain is a common condition of pregnancy, affecting a reported 20% of pregnant women. The pathophysiology is poorly understood and likely multifactorial, involving both hormonal and biomechanical changes that occur during pregnancy. Several risk factors have been identified. This diagnosis is most commonly made based on symptoms related to pelvic pain during pregnancy. Treatment should be multimodal, including pelvic girdle support, stabilizing exercises, analgesia, and potentially complementary therapies. The effects on future pregnancies are uncertain, although some limited information suggests an increased risk of recurrent PGP in subsequent pregnancies. Pelvic girdle pain in pregnancy is a common condition that is often overlooked as a normal part of pregnancy but has a significant impact on quality of life during, after, and in subsequent pregnancies. Multimodal therapies are available and are largely low cost and noninvasive. Our aim is to increase the awareness of pelvic girdle pain in pregnancy as a common but often underdiagnosed and undertreated condition.


The effects of infusions of arginine vasopressin or 1-deamino-8-D-arginine vasopressin on common carotid vascular resistance in conscious, Long Evans rats.
1. Intravenous infusions of arginine vasopressin or 1-deamino-8-D-arginine vasopressin (DDAVP) were given to conscious, Long Evans rats chronically instrumented with bilateral, common carotid, pulsed Doppler probes and intravascular catheters. 2. During infusion of vasopressin at 0.3 nmol min-1 there was an increase in common carotid vascular resistance with no change in mean blood pressure or heart rate. Following infusion there was a common carotid vasodilatation. 3. During infusion of vasopressin at 3.0 nmol min-1 there were increases in mean arterial blood pressure and in common carotid vascular resistances, accompanied by bilateral reductions in flow and in heart rate. Administration of (+)-(CH2)5Tyr(Et)DAVP (a V1-receptor antagonist), during the continued infusion of vasopressin, reversed the effects of the latter on mean blood pressure and heart rate; under these conditions there were increases in common carotid blood flows above baseline, in company with bilateral vasodilatations. The latter effects persisted after cessation of vasopressin infusion. 4. Infusions of DDAVP were without significant effects on any measured cardiovascular variable. 5. The results do not provide straightforward support for the claim that vasopressin acts to promote cerebral perfusion, at least when V1-receptor effects are unopposed. Furthermore, it seems likely tha the vasodilator influence of vasopressin on the common carotid vascular bed is not due to stimulation of V2-receptors.


Esophageal Motility Patterns in Paraesophageal Hernia Patients Compared to Sliding Hiatal Hernia: Bigger Is Not Better.
In patients with paraesophageal hernias (PEH), the course of the esophagus is often altered, which may affect esophageal motility. High-resolution manometry (HRM) is frequently used to evaluate esophageal motor function prior to PEH repair. This study was performed to characterize esophageal motility disorders in patients with PEH as compared to sliding hiatal hernia and to determine how these findings affect operative decision-making. Patients referred for HRM to a single institution from 2015 to 2019 were included in a prospectively maintained database. HRM studies were analyzed for the appearance of any esophageal motility disorder using the Chicago classification. PEH patients had confirmation of their diagnosis at the time of surgery, and the type of fundoplication performed was recorded. They were case-matched based on sex, age, and BMI to patients with sliding hiatal hernia who were referred for HRM in the same period. There were 306 patients diagnosed with a PEH who underwent repair. When compared to case-matched sliding hiatal hernia patients, PEH patients had higher rates of ineffective esophageal motility (IEM) (p<.001) and lower rates of absent peristalsis (p=.048). Of those with ineffective motility (n=70), 41 (59%) had a partial or no fundoplication performed during PEH repair. PEH patients had higher rates of IEM compared to controls, possibly due to a chronically distorted esophageal lumen. Offering the appropriate operation hinges on understanding the involved anatomy and esophageal function of each individual. HRM is important to obtain preoperatively for optimizing patient and procedure selection in PEH repair.


Nontraditional Occupational Exposures to Crude Oil Combustion Disasters and Respiratory Disease Risk: A Narrative Review of Literature.
Burning of petroleum products has been consistently associated with adverse respiratory health effects. Combustion of crude oil, specifically, produces toxic byproducts, but there have been relatively few studies of health effects. Burning of crude oil is increasingly employed as a means of mitigating environmental disasters despite the potential health risks to workers involved in clean-up efforts. Here, we review epidemiological studies of respiratory effects following unique crude oil burning events to (1) characterize respiratory health effects from this nontraditional occupational exposure and (2) identify approaches used to characterize exposures that could be applied to future disaster-related studies. We searched PubMed and EMBASE for references from inception to January 30, 2023. We also manually screened references cited in eligible articles. We identified 14 eligible publications. Our review suggests that exposure to crude oil combustion has adverse respiratory effects, including reduced lung function and increased occurrence of respiratory symptoms and disease. However, the evidence is inconsistent, and quality of data varied across studies. While some studies used quantitative, modeled exposure estimates, most used self-reported proxies of exposure. Although disasters involving crude oil combustion are relatively rare, limited evidence suggests that some worker populations may be at risk for respiratory effects from burning exposures in disaster settings. Future studies that use improved exposure assessment methods (e.g., personal monitors, remote sensing data) may help further quantify the respiratory risk from crude oil burning exposures.


Mental stress, meditation, and yoga in cardiovascular and cerebrovascular diseases.
It is well known that stress can increase the risk of heart attack and stroke although the exact way it does this is unknown. This information is particularly more relevant in a post COVID-19 era where healthcare workers are increasingly facing more stressful working conditions. Thus, it is important to look into alternative methods to deal with stress including meditation and yoga which have shown potential.


Evaluation of diabetic patients after three month use of continuous subcutaneous insulin infusion, dispensed by a protocolled form at outpatient reference clinic of Taguatinga Regional Hospital.
To evaluate the data of continuous subcutaneous insulin infusion protocol (CSII) for diabetics waived by the Health State Secretariat of Distrito Federal (HSSDF) and therapeutic responses three months after the transfer of multiple daily injections regimen for CSII. Eighty patients (49 female) took part in this experimental study, mean age and disease duration were 27.9 years and 13 years, respectively; 96% patients had type 1 diabetes mellitus. The entire sample (ECO) and 3 subgroups (group 1 - A1c decrease, group 2 - A1c stable, and group 3 - A1c increase), stratified according to a ≥ 0.5% change in A1c, were analyzed. Group 1 involved 64% of the patients. The ECO showed a significant A1c decrease: MDI 8.1 ± 1.4% vs. CSII 7.3 ± 0.9%, p < 0.0001 (0.8% difference pro CSII therapy). Group 1 demonstrated an A1c decrease from 8.7% to 7.3% (1.4% difference). Group 2 mean A1c was 7.1%. Rate of hypoglycemia (< 50 mg/dL) decreased 61% in the ECO and 79% in Group 2. This study reinforces the safety and efficacy of CSII with a robust A1c reduction and hypoglycemia. The pioneer care HSSDF ambulatory attests to be achievable the free dispensing by Unified Health System (UHS) following a protocol, and this approach results in less wastage to the patient and represents a rational policy of therapy with CSII for UHS.


Efficient construction of proline-containing β-turn mimetic cyclic tetrapeptides via CuAAC macrocyclization.
A range of macrocyclic β-turn mimetic tetrapeptides was prepared by efficient copper-tris(triazole) ligand complex catalyzed azide-alkyne "click" macrocyclizations in good to high yields. Preliminary conformational studies using X-ray crystallography and NMR spectroscopy demonstrated the presence of intramolecular H-bonds characteristic of β-turns in these cyclic tetrapeptides.


Time delay induced transition of gene switch and stochastic resonance in a genetic transcriptional regulatory model.
Noise, nonlinear interactions, positive and negative feedbacks within signaling pathways, time delays, protein oligomerization, and crosstalk between different pathways are main characters in the regulatory of gene expression. However, only a single noise source or only delay time in the deterministic model is considered in the gene transcriptional regulatory system in previous researches. The combined effects of correlated noise and time delays on the gene regulatory model still remain not to be fully understood. The roles of time delay on gene switch and stochastic resonance are systematically explored based on a famous gene transcriptional regulatory model subject to correlated noise. Two cases, including linear time delay appearing in the degradation process (case I) and nonlinear time delay appearing in the synthesis process (case II) are considered, respectively. For case I: Our theoretical results show that time delay can induce gene switch, i.e., the TF-A monomer concentration shifts from the high concentration state to the low concentration state ("on"→"off"). With increasing the time delay, the transition from "on" to "off" state can be further accelerated. Moreover, it is found that the stochastic resonance can be enhanced by both the time delay and correlated noise intensity. However, the additive noise original from the synthesis rate restrains the stochastic resonance. It is also very interesting that a resonance bi-peaks structure appears under large additive noise intensity. The theoretical results by using small-delay time-approximation approach are consistent well with our numerical simulation. For case II: Our numerical simulation results show that time delay can also induce the gene switch, however different with case I, the TF-A monomer concentration shifts from the low concentration state to the high concentration state ("off"→"on"). With increasing time delay, the transition from "on" to "off" state can be further enhanced. Moreover, it is found that the stochastic resonance can be weaken by the time delay. The stochastic delay dynamic approach can identify key physiological control parameters to which the behavior of special genetic regulatory systems is particularly sensitive. Such parameters might provide targets for pharmacological intervention. Thus, it would be highly interesting to investigate if similar experimental techniques could be used to bring out the delay-induced switch and stochastic resonance in the stochastic gene transcriptional regulatory process.


Cranial computed tomography 2: use in clinical practice.
The importance of cranial computed tomography in the diagnosis and follow up of intracranial pathology cannot be underestimated. Clinicians at every level should have a basic understanding of this technique. This second part discusses the practical use of computed tomography in the clinical setting.


Is severity of Daboia (Vipera) palaestinae snakebites influenced by season of exposure?
The most common venomous snake in Israel, both in geographic spread and in number of snakebite incidents, is Daboia (Vipera) palaestinae. The clinical presentation of D. palaestinae envenomation varies and includes both local and systemic symptoms. Studies conducted on D. palaestinae revealed different amounts of venom in the snakes' glands in different seasons, however little is known regarding the potential impact of this finding on the clinical presentation after D. palaestinae bites during different seasons. To evaluate whether there is a difference in the severity of the clinical presentation of D. palaetinae bites in different seasons. A retrospective chart review study including all patients diagnosed with D. palaestinae bites treated at Shamir Medical Center from 2006 through 2020. Patients were divided into two groups: early bite season - spring and early summer, and late bite season - late summer and autumn. Variables examined included demographic features, admission details and treatment administrated. One hundred and seven D. palaestinae bite victims were included, forty-five were bitten during the early season and sixty-two during the late season. Four patients in the early season (8.9%) and one patient (1.6%) in the late season presented with decreased level of consciousness, and four patients, all from the early season group, required mechanical ventilation (p < 0.05) Vasopressors were used in six patients (13.3%) during the early season and two (3.2%) during the late season; (p = 0.06). There were no other differences between the groups, except for a lowest platelet count during hospitalization (mean 161.5 ± 51 K/μl during early season and 196.9 ± 77 K/μl during late season (p < 0.01). D. palaestinae bite victims more often present as critically ill patients during the spring and early summer compared to late summer and autumn. Hospitals should be prepared with appropriate staff training and medications for treating such patients, especially during the early season. However, in general, D. palaestinae bites are as dangerous during the late season as they are during the early season, and all snake bite victims should be treated with a high index of suspicion regardless of the season.


A factor analytic study of branching patient management problems.
This study was undertaken to determine the factor analytic structure of patient management problems (PMPs) and to determine whether such factors are stable for different groups taking the same examination and for the same group over time. Two examinations were administered to a group of medical students, the first during their junior year and the second during their senior year. The second examination was also administered to a second class of students during their junior year. Factor analyses results indicated there are two components to medical problem-solving as measured by PMPs-data gathering and management. Both factors were stable over groups and over time.


Tannic acid functionalized graphene hydrogel for organic dye adsorption.
Water purification provides a feasible way to relieve the pressure of water shortage and water pollution which we are facing and adsorption is one of the most effective ways to turn polluted water into clean water. Here, we prepared graphene-tannic acid hydrogel using graphene oxide and tannic acid, a natural green reducer and adsorbent, through one-step hydrothermal method. The composition, structure, and morphology of the compounds were systematically examined. The adsorption of dyes was mainly influenced by the morphology and chemical properties of gel. The addition of tannic acid, a molecule rich in oxygen containing functional groups, changed the surface chemistry of graphene sheets and microstructures of gels, which was beneficial for contaminate adsorption. Compared with reduced graphene oxide hydrogel, the graphene-tannic acid hydrogel showed an outstanding adsorption capacity for organic dye methylene blue, more than 500 mg/g at pH 10 and the maximum adsorption capacity was up to 714 mg/g. After adsorption, ethanol and inorganic acid solution can be used as desorption agent and there was no significant adsorption capacity loss after 5 cycles.


Serotonin-3 receptor and ethanol-stimulated dopamine release in the nucleus accumbens.
The present study was undertaken to examine the involvement of activation of 5-HT3 receptors in the rat nucleus accumbens (Acb) on the effects of ethanol-induced increases of dopamine (DA) using the selective agonist 1-(m-chlorophenyl)-biguanide (CPBG). Perfusion of CPBG through the microdialysis probe concentration-dependently (3.3-100 microM) enhanced the extracellular levels of DA in the Acb. Extracellular DA concentrations increased as high as 1000% of baseline. The CPBG-induced increases in DA levels were Ca++ dependent and inhibited by local perfusion with the 5-HT3 antagonist ICS 205-930 (100 microM). In addition, CPBG at high concentrations caused significant decreases in the extracellular levels of DA metabolites. Intraperitoneal (IP) injection of 1 g/kg ethanol produced no changes in extracellular DA levels in the Acb; coadministration of 1 g/kg ethanol (IP) and 5 microM CPBG (local) produced increases equal to 5 microM CPBG alone. Administration of 2 g/kg ethanol (IP) alone enhanced extracellular DA levels by approximately 60% above baseline, whereas local perfusion of 5 microM CPBG alone produced an increase of approximately 100% above baseline. The coadministration of 2 g/kg ethanol (IP) and 5 microM CPBG (local) enhanced DA levels by approximately 170% above baseline; this apparent additive enhancement was almost completely prevented when 100 microM ICS 205-930 was locally coperfused. Local administration of 3.3-100 microM CPBG did not alter the extracellular levels of serotonin or 5-hydroxyindoleacetic acid. The results support an involvement of 5-HT3 receptors in regulating DA release in the Acb, and also in mediating ethanol-induced DA release.(ABSTRACT TRUNCATED AT 250 WORDS)


Multicenter evaluation of the Verigene Gram-negative blood culture nucleic acid test for rapid detection of bacteria and resistance determinants in positive blood cultures.
The Verigene Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) is a microarray-based assay that enables rapid detection of 9 common Gram-negative bacteria and 6 resistance determinants directly from positive blood cultures. We compared the performance of BC-GN with currently used automated systems, testing 141 clinical blood cultures and 205 spiked blood cultures. For identification of BC-GN target organisms in clinical and spiked blood cultures, the BC-GN assay showed 98.5% (130/132) and 98.9% (182/184) concordance, respectively. Of 140 resistance genes positively detected in clinical and spiked blood cultures with the BC-GN test, 139 (99.3%) were confirmed by PCR, and the detection results were consistent with the resistance phenotypes observed. The BC-GN assay, thus, can potentially improve care for sepsis patients by enabling timely detection and targeted antimicrobial therapy.


The identification of the N tau-methyl histidine-containing dipeptide, balenine, in muscle extracts from various mammals and the chicken.
The occurrence of the dipeptide, balenine (beta-alanyl-N tau-methyl histidine), has been identified by comparative chromatography in extracts of muscles from 9 species of mammal, including man, and the chicken. The identity of the dipeptide from 6 mammalian species and chicken was confirmed by preparative isolation prior to determination of the amino acid composition and N-terminal residue. In all cases, the dipeptide contained equimolar amounts of beta-alanine and N tau-methyl histidine with beta-alanine as the N-terminus. The concentration of the dipeptide varied dramatically between species, being just detectable in the muscle of man and rat while present at concentrations of up to 14 mumol/g wet muscle in adult pigs. It is proposed that balenine, like carnosine and anserine, should be regarded as a normal constituent of muscle.


Neighbourhood ethnic density and psychosis - Is there a difference according to generation?
For different migrant groups living in an area with few people from the same ethnic background is associated with increased psychosis incidence (the ethnic density effect). We set out to answer the question: are there generational differences in this effect? Analysis of a population based cohort (2.2 million) comprising all those born 1st January 1965, or later, living in Denmark on their 15th birthday. This included 90,476 migrants from Africa, Europe (excluding Scandinavia) and the Middle East, with 55% first generation and the rest second-generation migrants. Neighbourhood co-ethnic density was determined at age 15 and we adjusted for age, gender, calendar period, parental psychiatric history and parental income. For first-generation migrants from Africa, there was no statistically significant difference (p=0.30) in psychosis rates when comparing lowest with highest ethnic density quintiles, whereas the second generation showed a 3.87-fold (95% CI 1.77-8.48) increase. Similarly, for migrants from the Middle East, the first generation showed no evidence of an ethnic density effect (p=0.94) while the second showed a clear increase in psychosis when comparing lowest with highest quintiles, incidence rate ratio (IRR) 2.43 (95% CI, 1.18-5.00). For European migrants, there was some limited evidence of an effect in the first generation, (IRR) 1.69 (95% CI, 1.19-2.40), with this slightly raised in the second: IRR 1.80 (95% CI, 1.27-2.56). We found strong evidence for an ethnic density effect on psychosis incidence for second-generation migrants but this was either weak or absent for the first generation.


The Integrated Review: FDA Modernizes the Review of New Drug Marketing Applications.
New Drug Applications and Biologics Licensing Applications submitted to the US Food and Drug Administration (FDA) are reviewed by an interdisciplinary team of regulatory scientists that includes medical officers, clinical pharmacologists, toxicologists, statisticians, and drug labeling experts. Upon review of an applicant's submitted evidence from nonclinical studies, clinical trials, and manufacturing capabilities, the review team evaluates the benefits and risks of the drug and makes a scientifically-informed decision. As part of a multi-year, multi-phase New Drugs Regulatory Program Modernization effort, the FDA has recently redesigned how it reviews and documents its decisions with regard to marketing applications. This article describes the origins and rationale of the new Integrated Assessment process and Integrated Review document, summarizes how these differ from the FDA's traditional review of marketing applications, and discusses what industry can expect from a modernized drug review.


Methodological problems in cross-cultural studies of linguistic relativity.
Bloom (1981) tested a weak version of the linguistic relativity hypothesis (i.e., "Language affects thinking though it does not determine thinking") in a series of cross-cultural experiments. According to Bloom, Chinese lacks two linguistic devices that are present in English and supposed to be critical in performing theoretical thinking. It was found that the Chinese subjects were outperformed by American counterparts in all the tests designed to assess the ability of theoretical thinking. The results were taken as evidence for the weak version of the linguistic relativity hypothesis. A methodological consideration has revealed, however, that all of his experiments except one are uninterpretable because of the lack of necessary control conditions. In addition, three experiments in the present study have demonstrated that the findings in Bloom's sole interpretable experiment were artifacts due to a methodological flaw. Further theoretical considerations reveal the inadequacy of Bloom's basic methodology and the limitation in the effects of linguistic relativity that may be possible at least theoretically.


Zinc uptake and phyto-toxicity: Comparing intensity- and capacity-based drivers.
Metal bioavailability and phytotoxicity may be exaggerated when derived from studies based on amending soils with soluble metal salts. It is therefore important to evaluate soil tests for their consistency in estimating plant uptake and phytotoxicity in both field-contaminated and freshly-spiked soils. This study aimed to compare the effects of zinc (Zn) on plant growth in soils (i) recently spiked with soluble Zn and (ii) historically amended with biosolids. The objective was to reconcile methods for determining bioavailability in both cases by testing a range of 'quantity-based' and 'intensity-based' assays. Soils with a range of Zn concentrations, from an arable farm used for biosolids disposal for over a century, were further amended with Zn added in solution, and were incubated for one month prior to planting with barley seeds in a glasshouse pot trial. The majority (67-90%) of the added Zn remained isotopically exchangeable after 60 days. Zinc in the solution phase of a soil suspension was present mainly as free Zn2+ ions. Cadmium bioaccumulation factors were inversely proportional to Zn concentration in the soil solution confirming that greater Zn availability suppressed Cd uptake by plants. Measurements of soil Zn 'quantities' (total, EDTA-extractable and isotopically exchangeable) and 'intensity' (solution concentration and free ion activity) were correlated with Zn uptake and toxicity by barley plants. Correlations using Zn intensity were much stronger than those using quantity-based measurements. The free Zn2+ ion activity appears to be a consistent driver for plant uptake and phytotoxic response for both metal-spiked soils and historically contaminated soils. Surprisingly, soil Zn accumulation of up to 100 times the current regulations for normal arable land only produced a mild toxic response suggesting that constituents in biosolids (e.g. organic matter and phosphates) strongly restrict metal bioavailability.


Ionization of Cp2 ZrMe2 and Lewis Bases by Methylaluminoxane: Computational Insights.
The interactions of the Lewis bases CO, octamethyltrisiloxane (OMTS) and 2,2'-bipyridine (bipy) with a sheet model for the principal activator (MeAlO)16 (Me3 Al)6 (16,6) in hydrolytic methylaluminoxane (MAO) were investigated by DFT. These studies reveal that OMTS and bipy form adducts with Me3 Al prior to methide abstraction by 16,6 to form the ion-pairs [Me2 Al(κ2 -L)][16,6] (5: L=OMTS, 6: L=bipy, [16,6]- =[(MeAlO)16 (Me3 Al)6 Me]- ) while CO simply binds to a reactive edge site without ionization. The binding and activation of Cp2 ZrMe2 with 16,6 to form both neutral adducts 1 Cp2 ZrMe2 ⋅16,6 and contact ion-pairs 4 and 7, both with formula [Cp2 ZrMe][μ-Me(MeAlO)16 (Me3 Al)6 ], featuring terminal and chelated MAO-anions, respectively was studied by DFT. The displacement of the anion with either excess Cp2 ZrMe2 or Me3 Al was also studied, forming outer-sphere ion-pairs [(Cp2 ZrMe)2 μ-Me][16,6] (2) and [Cp2 Zr(μ-Me)2 AlMe2 ][16,6] (3). The theoretical NMR spectra of these species were compared to experimental spectra of MAO and Cp2 ZrMe2 and found to be in good agreement with the reported data and assignments. These studies confirm that 16,6 is a very suitable model for the activators present in MAO but highlight the difficulty in accurately calculating thermodynamic quantities for molecules in this size regime.


5-[(1,3-Dimethyl-5-oxo-2-sulfanylideneimidazolidin-4-yl-idene)amino]-2-methyl-isoindoline-1,3-dione.
The title N,N-di-methyl-thio-hydantoin containing an N-methyl-ated pthalimide group, C14H12N4O3S, arose from an unexpected reaction in a deep eutectic di-methyl-thio-urea-tartaric acid solvent system. The mean planes of the ring systems are twisted at an angle of 73.84 (17)°. In the crystal, weak C-H⋯O hydrogen bonds connect the mol-ecules.


Calculated LET spectrum from antiproton beams stopping in water.
Antiprotons have been proposed as a potential modality for radiotherapy because the annihilation at the end of range leads to roughly a doubling of physical dose in the Bragg peak region. So far it has been anticipated that the radiobiology of antiproton beams is similar to that of protons in the entry region of the beam, but very different in the annihilation region, due to the expected high-LET components resulting from the annihilation. On closer inspection we find that calculations of dose averaged LET in the entry region may suggest that the RBE of antiprotons in the plateau region could significantly differ from unity, which seems to warrant closer inspection of the radiobiology in this region. Monte Carlo simulations using FLUKA were performed for calculating the entire particle spectrum of a beam of 126 MeV antiprotons hitting a water phantom. In the plateau region of the simulated antiproton beam we observe a dose-averaged unrestricted LET of about 4 keV/microm, which is very different from the expected 0.6 keV/microm of an equivalent primary proton beam. Even though the fluence of secondaries is a magnitude less than the fluence of primary particles, the increased stopping power of the secondary particles causes an increase in the dose averaged LET which is expected to result in a RBE different from unity.


Management of severe reflux in the patient with cyclophosphamide cystitis.
Cyclophosphamide cystitis with a high grade of vesicoureteral reflux can lead to rapid renal deterioration. Conventional ureteral reimplantation is inadvisable and urinary diversion, although providing a temporary solution, could lead to long-term complications, particularly in children. We present a case of cyclophosphamide cystitis with vesicoureteral reflux and upper tract deterioration managed successfully with ileocecocystoplasty. This method of management should be considered early in such a patient.


Ruthenium(II) polypyridyl complexes as mitochondria-targeted two-photon photodynamic anticancer agents.
Clinical acceptance of photodynamic therapy is currently hindered by poor depth efficacy and inefficient activation of the cell death machinery in cancer cells during treatment. To address these issues, photoactivation using two-photon absorption (TPA) is currently being examined. Mitochondria-targeted therapy represents a promising approach to target tumors selectively and may overcome the resistance in current anticancer therapies. Herein, four ruthenium(II) polypyridyl complexes (RuL1-RuL4) have been designed and developed to act as mitochondria-targeted two-photon photodynamic anticancer agents. These complexes exhibit very high singlet oxygen quantum yields in methanol (0.74-0.81), significant TPA cross sections (124-198 GM), remarkable mitochondrial accumulation, and deep penetration depth. Thus, RuL1-RuL4 were utilized as one-photon and two-photon absorbing photosensitizers in both monolayer cells and 3D multicellular spheroids (MCSs). These Ru(II) complexes were almost nontoxic towards cells and 3D MCSs in the dark and generate sufficient singlet oxygen under one- and two-photon irradiation to trigger cell death. Remarkably, RuL4 exhibited an IC50 value as low as 9.6 μM in one-photon PDT (λirr = 450 nm, 12 J cm(-2)) and 1.9 μM in two-photon PDT (λirr = 830 nm, 800 J cm(-2)) of 3D MCSs; moreover, RuL4 is an order of magnitude more toxic than cisplatin in the latter test system. The combination of mitochondria-targeting and two-photon activation provides a valuable paradigm to develop ruthenium(II) complexes for PDT applications.


Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease.
Endogenous matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are important mediators of extracellular matrix remodeling, which is integral to plaque progression in coronary artery disease. In addition, high levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. We hypothesized that circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were abnormal in patients who had stable coronary artery disease, and these levels were compared with those in matched controls. We also hypothesized correlations of MMPs, TIMPs, and sCD40L to each other and to high-sensitivity C-reactive protein (a proinflammatory marker), white blood cell count, severity of coronary artery disease (based on angiographic measurements of atherosclerotic burden), and coronary collateralization. We studied 204 adult patients who attended our unit for outpatient diagnostic cardiac catheterization for the investigation of suspected coronary artery disease. Coronary angiograms were scored for atheroma burden and stenosis by 2 independent observers. Circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were measured by enzyme-linked immunosorbent assay. Plasma levels of MMP-9 (p = 0.0099), TIMP-2 (p = 0.0019), and sCD40L (p <0.001), but not TIMP-1 (p = 0.463) were high in patients compared with healthy controls. In patients who had coronary artery disease, MMP-9 and high-sensitivity C-reactive protein levels were significantly higher in women than in men. Only MMP-9 correlated modestly with total white blood cell count (Spearman's correlation, r = 0.274, p = 0.002). Logistic regression of cardiovascular risk factors showed that only white blood cell count was independently associated with MMP-9 (p = 0.02). After standardizing for atheroma and stenosis scores, there were no statistically significant differences in our research indexes in patients who had angiographic collaterals compared with those who did not. In conclusion, stable coronary artery disease is associated with abnormal circulating levels of MMP-9, TIMP-2, and sCD40L, which do not appear to related to each other or to severity of coronary artery disease or collateralization. The gender difference in high-sensitivity C-reactive protein and MMP-9 levels may provide insight into the pathophysiology of coronary artery disease in men and women, and further studies are warranted to explore this potential link.


Cost of territory establishment in hummingbirds.
Time spent in territorial defense was measured during territory establishment for non-breeding Black-chinned (Archilochus alexandri) and Anna's (Calypte anna) hummingbirds. Newly established territory holders spent more time chasing intruders than neighboring established owners, which served as controls. This higher investment in defense by the new owners was due to 1) a longer time spent per each chase and 2) in some cases, a higher frequency of chases at the onset of territory ownership.


Experimental study of electrical FitzHugh-Nagumo neurons with modified excitability.
We present an electronical circuit modelling a FitzHugh-Nagumo neuron with a modified excitability. To characterize this basic cell, the bifurcation curves between stability with excitation threshold, bistability and oscillations are investigated. An electrical circuit is then proposed to realize a unidirectional coupling between two cells, mimicking an inter-neuron synaptic coupling. In such a master-slave configuration, we show experimentally how the coupling strength controls the dynamics of the slave neuron, leading to frequency locking, chaotic behavior and synchronization. These phenomena are then studied by phase map analysis. The architecture of a possible neural network is described introducing different kinds of coupling between neurons.


Identification of differential genomic DNA Methylation in the hypothalamus of pubertal rat using reduced representation Bisulfite sequencing.
There are many variables affecting the onset of puberty in animals, including genetic, nutritional, and environmental factors. Recent studies suggest that epigenetic regulation, especially DNA methylation, plays a majorrole in the regulation of puberty. However, there have been no reports on DNA methylation of the pubertal genome. We investigated DNA methylation in the female rat hypothalamus at prepuberty and puberty using reduced representation bisulfite sequencing technology. The identified genes and signaling pathways exhibiting changes to DNA methylation in pubertal rats were determined by Gene Ontogeny and Kyoto Encyclopedia of Genes and Genomes analysis. The distribution of the three types of methylated C bases in promoter and CpG island (CGI) regions in the hypothalamus was as follows: 87.79% CG, 3.05% CHG, 9.16% CHH for promoters, and 88.35% CG, 3.21% CHG, 88.35% CHH for CGI in prepubertal rats; and 90.78% CG, 2.13% CHG, 7.09% CHH for promoters, and 88.59% CG, 88.59% CHG, 8.35% CHH for CGI in pubertal animals. CG showed the highest percentage of methylation, and was the highest methylation state in CGI. Compared to prepubertal hyoyhalamus samples, we identified ten genes with altered methylation in promoter regions in the pubertal hypothalamus samples, and 43 genes with altered methylation in the CGI. Changes in DNA methylation were found in gonadotropin-releasing hormone signaling pathways, and the oocyte meiosis pathway. Our results demonstrate changes in DNA methylation occur in female rats from prepuberty to puberty suggestng DNA methylation may play a crucial role in the regulation of puberty onset. This study provides essential information for future studies on the role of epigenetics in the regulation of puberty.


Screening and surveillance of pregnancy hypertension--an economic approach to the use of daycare.
Frequent measurement of blood pressure is an accepted part of routine outpatient antenatal care. Women found to have mild hypertension may be further monitored for signs of progressive disease, while women with proteinuria or severe hypertension may be admitted for more intensive surveillance or treatment. In practice, the course and ultimate severity of this disorder are unpredictable and women with mild hypertension are frequently admitted. Recently, daycare has grown as an option for assessing women with hypertension as it offers the advantage of more extensive evaluation than is possible at an outpatient clinic and is widely assumed to be more cost-effective than conventional management. However, its use in obstetrics has not been subject to a formal economic appraisal. Such an evaluation is currently being carried out in two hospitals in Scotland, one of which uses daycare and inpatient admissions in the management of hypertension and one of which uses domiciliary midwife visits as well as hospital beds. Preliminary results suggest that the pregnancy outcome in terms of birthweight, gestation at delivery, admission to a special unit, etc., are the same in the two units for women with mild hypertension (diastolic 90-99 mmHg, no proteinuria). The costs per patient were less in the hospital with a daycare unit. These lower individual costs, however, do not mean that the overall costs to the health service are less in a hospital with daycare. This will depend on the average number of visits to daycare for women with mild hypertension, the proportion of hypertensive women receiving daycare, whether freed inpatient beds are closed or redeployed, and the capital costs of establishing a day unit. Data has also been collected on women's costs and views which will ultimately be presented and should play a part in any decision to implement or continue daycare.


Residential mobility in early childhood and obesity at kindergarten age among children from the United States.
Children who frequently move have poorer behavioural, emotional, and overall health. For similar reasons, the experience of changing home may contextualize children's risk for obesity. Few studies have assessed the relationship between residential mobility and obesity; even fewer explore this relationship with assessment of obesity before school age. We analysed data from the Early Childhood Longitudinal Study-Birth Cohort. Obesity at kindergarten age was determined from measured height and weight. Early childhood residential mobility was categorized as not moving or having moved once, twice, or three or more times. Analyses are weighted to be representative of children from the United States and variance estimates account for the complex survey design. The prevalence of obesity at kindergarten age was 17.5%, and most children (71%) moved in early childhood. Compared with children who did not move, the adjusted odd ratios for obesity at kindergarten age were 0.72 (95% CI, 0.57-0.92), 0.70 (95% CI, 0.55-0.89), and 0.64 (95% CI, 0.50-0.84) for children who experienced 1, 2, or 3+ moves. Our study suggests that obesity and mobility in early life are associated, but not in the way we might expect. Residential mobility may fit into a broader picture of instability and, on its own, may not elevate a child's risk for obesity.


Subjective cognitive decline, anxiety symptoms, and the risk of mild cognitive impairment and dementia.
Subjective cognitive decline (SCD) and anxiety symptoms both predict neurocognitive disorders, but the two correlate strongly with each other. It is unclear whether they reflect two independent disease processes in the development of neurocognitive disorders and hence deserve separate attention. This cohort study examined whether SCD and anxiety symptoms demonstrate independent risks of mild cognitive disorder and dementia (MCI/dementia). The study included 14,066 participants aged ≥ 50 years and diagnosed with normal cognition at baseline, recruited from Alzheimer's Disease Centers across the USA. The participants were evaluated for SCD and anxiety symptoms at baseline and followed up almost annually for incident MCI/dementia (median follow-up 4.5 years; interquartile range 2.2-7.7 years). SCD and anxiety symptoms were included in Cox regression to investigate their independent risks of MCI/dementia. SCD and anxiety symptoms demonstrated independent risks of MCI/dementia, with HR 1.9 (95% CI 1.7-2.1) and 1.3 (95% CI 1.2-1.5), respectively. Co-occurring SCD and anxiety symptoms demonstrated the highest risk (HR 2.4, 95% CI 1.9-2.9)-participants in this group had a 25% probability of developing MCI/dementia by 3.1 years (95% 2.4-3.7), compared to 8.2 years among those without SCD or anxiety (95% CI 7.9-8.6). The results remained robust even in the sensitivity analyses that took into account symptom severity and consistency of symptoms in the first 2 annual visits. The findings suggest that clinicians should not dismiss one over the other when patients present with both SCD and anxiety and that both constructs may potentially be useful to identify high-risk populations for preventive interventions and trials. The findings also point to the need for further research to clarify on the neurobiological distinctions between SCD and anxiety symptoms, which may potentially enrich our understanding on the pathogenesis of neurocognitive disorders.


TRIM40 ameliorates diabetic retinopathy through suppressing inflammation via Reelin/DAB1 signaling disruption: A mechanism by proteasomal degradation of DAB1.
Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Reelin, an extracellular matrix protein, and its effector protein Disabled1 (DAB1) have been linked to cellular events and retinal development. However, whether and how Reelin/DAB1 signaling causes DR remains to be investigated. In our study, significantly increased expression of Reelin, very low density lipoprotein receptor (VLDLR), ApoE receptor 2 (ApoER2) and phosphorylated DAB1 in retinas of streptozotocin (STZ)-induced DR mouse model was observed, along with enhanced expression of proinflammatory factors. Similar results are confirmed in high glucose (HG)-treated human retinal pigment epithelium cell line ARPE-19. Surprisingly, dysregulated tripartite motif-containing 40 (TRIM40), an E3 ubiquitin ligase, is found to be involved in DR progression by bioinformatic analysis. We observe a negative correlation between TRIM40 and p-DAB1 protein expression levels under HG conditions. Importantly, we find that TRIM40 over-expression markedly ameliorates HG-induced p-DAB1, PI3K, p-protein B kinase (AKT) and inflammatory response in HG-treated cells, but dose not affect Reelin expression. Of note, Co-IP and double immunofluorescence identify an interaction between TRIM40 and DAB1. Furthermore, we show that TRIM40 enhances K48-linked polyubiquitination of DAB1, thereby promoting DAB1 degradation. Finally, promoting TRIM40 expression by intravenous injection of the constructed adeno-associated virus (AAV-TRIM40) markedly ameliorates DR phenotypes in STZ-treated mice, as indicated by the decreased blood glucose and glycosylated hemoglobin (HbAlc) levels, and increased hemoglobin contents. Additionally, diabetes-related elevation of acellular capillaries was also meliorated in mice over-expressing TRIM40. The electroretinogram (ERG) deficits were strongly rescued in mice receiving AAV-TRIM40 injection. Moreover, AAV-TRIM40 attenuates the inflammation and p-DAB1 expression in retinal tissues of STZ-treated mice. Collectively, our findings disclose a mechanism through which TRIM40 limits DAB1 stability under physiological conditions and reveals TRIM40 as a potential therapeutic target for the intervention of Reelin/DAB1 signaling, contributing to DR treatment.


Artifacts in magnetic resonance imaging after surgical resection of brain tumors.
Since the advent of magnetic resonance imaging, metal artifacts have posed an important diagnostic problem in different fields of medicine. However, this has not been systematically studied in patients undergoing surgery for brain tumors. This study was planned to assess whether metal artifacts can occur in patients undergoing brain surgery without metallic implants. Of 40 individuals who could be included because of having a pre- and postoperative MRI and a postoperative computed tomography (CT) scan or a conventional skull X-ray for the detection of metallic artifacts, 26 patients agreed to participate in this study and gave informed consent. Twenty-six subjects, 12 males and 14 females, with an age range of 12 to 54 years, were included in the study. Four patients were found to have gross metal particles in their postoperative brain CTs and were excluded. Of the remaining 22 subjects, 7 patients (31.8%) had metallic artifacts. Our study showed that simple bone drilling or chiseling during surgical manipulation of skull bones may result in separation of very tiny metal particles which can remain in the surgical site and cause artifacts in postoperative MRIs. This finding appeared to be independent of factors such as age, sex, tumor/incision site, tumor size, pathologic tumor type, total radiation dose, operation-MRI time interval and sequence of MRI.


Inflammatory cell profiles and T-lymphocyte subsets in chronic obstructive pulmonary disease and severe persistent asthma.
Severe persistent asthma (SPA) and chronic obstructive pulmonary disease (COPD) are both associated with non-reversible airflow limitation and airway neutrophilia. To compare inflammatory cell profiles and T lymphocyte subsets between SPA and COPD patients with similar severity of airflow limitation. Sputum induction and lung function tests were performed in 15 COPD patients aged (mean+/-SD) 68+/-8 years, ex-smokers, mean forced expiratory volume in 1 s (FEV1) 45% of predicted (% pred) and 13 SPA aged 55+/-10 years, non-smokers, mean FEV(1) 49% pred. All patients were on inhaled steroid treatment. Eight asthmatics exhibited irreversible airflow limitation. Differential cell count, metachromatic cell count and double immunocytochemistry for the analysis of T lymphocyte subsets were performed on sputum slides. COPD patients had increased sputum neutrophils in comparison with SPA (P<0.03), but similar to SPA with fixed obstruction. In COPD sputum neutrophils negatively correlated with the lung transfer factor for carbon monoxide (KCO) (r=-0.462, P=0.04). SPA showed significantly increased eosinophils and metachromatic cells vs. COPD patients (P<0.04, P<0.007, respectively). Increased CD4/CD8 and decreased CD4-IFN-gamma/CD4-IL4+ cell ratio (P<0.001) were found in SPA vs. COPD. In SPA, CD4/CD8+ cell ratio correlated with sputum eosinophils (r=0.567, P=0.04). In spite of treatment with inhaled steroids, SPA and COPD exhibit distinct sputum inflammatory cell patterns, although SPA with fixed airflow limitation and COPD patients have similar numbers of neutrophils.


Targeting of GIT1 by miR-149* in Breast Cancer Suppresses Cell Proliferation and Metastasis in vitro and Tumor Growth in vivo [Retraction].
[This retracts the article DOI: 10.2147/OTT.S144280.].


[Structural magnetic resonance imaging in epilepsy].
Magnetic resonance imaging is the main structural imaging in epilepsy. In patients with focal seizures, detection (and characterization) of a structural lesion consistent with electroclinical data allows therapeutic decisions without having to resort to other more expensive or invasive diagnostic procedures. The identification of some lesions may provide prognostic value, as in the case of Mesial Temporal Sclerosis (MTS) or may contribute to genetic counseling, as in the case of some Malformations of Cortical Development (MCD). The aim of this paper is to review the current state of structural MRI techniques, propose a basic protocol of epilepsy and mention the indications for structural MRI. Also, review the semiology of the main causes of epilepsy, with emphasis on MTS and MCD, by its highest frequency and by the special impact that MRI has shown in dealing with these entities.


Intracellular cAMP determines the extent of degradation and not the synthesis of collagen by rat hepatocytes.
Intracellular collagen degradation in normal rat hepatocytes was exponentially stimulated by db-cAMP (10-100 microM). The effect was manifested as a decrease (p less than 0.01) in net collagen production. The extent of degradation directly co-related with the intracellular cAMP levels, only up to a threshold concentration (16.2 +/- 1.3 p moles/10(6) cells) elicited by 100 microM of db-cAMP. Higher concentrations induced no further increment. Forskolin adenylate cyclase activator (10-50 microM), produced similar effects demonstrating cAMP dependence of the phenomenon. Both db-cAMP as well as Forskolin stimulated collagen degradation (p less than 0.05) in hepatocytes from rats administered CCL4. However, the extent of stimulation was significantly (p less than 0.01) less compared to that observed in normal hepatocytes. Our data demonstrates that elevated cAMP levels regulate net collagen content by signalling intracellular collagen degradation and not synthesis.


Factor structure and construct validity of "what I think and feel": The Revised Children's Manifest Anxiety Scale.
Responses to the Revised-CMAS of 329 children from grades 1 through 12 were factor analyzed. Consistent with current multidimensional theories of anxiety, three primary anxiety factors emerged, supporting the construct validity of the new scale. Implications for interpretation of the revised scale are discussed.


Effects of antioxidant gene therapy on retinal neurons and oxidative stress in a model of retinal ischemia/reperfusion.
Retinal ischemia/reperfusion (I/R) results in neuronal death and generation of reactive oxygen species. The aim of this study was to investigate the neuroprotective effect of manganese superoxide dismutase (SOD2) on retinal ganglion cells (RGCs) in an I/R-induced retinal injury model. One eye of each Wistar rat was pretreated with recombinant adeno-associated virus containing the SOD2 gene (AAV-SOD2) or recombinant AAV containing the GFP gene (AAV-GFP) by intravitreal injection 21 days before initiation of I/R injury. Retinal I/R injury was induced by elevating intraocular pressure for 1h, and reperfusion was established immediately afterward. The number of RGCs and the inner plexiform layer (IPL) thickness were measured by Fluorogold retrograde labeling and hematoxylin and eosin staining at 6 h, 24 h, 72 h, and 5 days after injury. Superoxide anion, the number of RGCs, IPL thickness, malondialdehyde (MDA) level, 8-hydroxy-2-deoxyguanosine (8-OHdG) level, MnSOD (manganese superoxide dismutase) activity, and nitrotyrosine level were measured by fluorescence staining, immunohistochemistry, and enzyme-linked immunosorbent analysis at 5 days after I/R injury. Severe RGC loss, reduced IPL thickness, reduced MnSOD activity, and increased superoxide ion, MDA, 8-OHdG, and nitrotyrosine production were observed after I/R injury. Administration of AAV-SOD2 significantly reduced the levels of superoxide ion, MDA, 8-OHdG, and nitrotyrosine and prevented the damage to RGCs and IPL. Delivery of the antioxidant gene inhibited I/R-induced RGC and IPL damage by reducing oxidative stress and nitrative stress, suggesting that MnSOD may be relevant for the neuroprotection of the inner retina from I/R-related diseases.


Potassium channel structures.
The molecular basis of K+ channel function is universally conserved. K+ channels allow K+ flux and are essential for the generation of electric current across excitable membranes. K+ channels are also the targets of various intracellular control mechanisms, such that the suboptimal regulation of channel function might be related to pathological conditions. Because of the fundamental role of K+ channels in controlling membrane excitability, a structural understanding of their function and regulation will provide a useful framework for understanding neuronal physiology. Many recent physiological and crystallographic studies have led to new insights into the workings of K+ channels.


The personal life of the behavior analyst.
The human species faces crises of critical proportions. Excessive population, global warming, and the anticipated descent from peak fossil-fuel extraction promise to change our future in far-reaching ways. Operant conditioning prepares the individual for a world similar to the selecting past, but our world is changing more rapidly than our adaptation. As individuals, we cannot make substantial changes in the world at large because we do not control enough reinforcers, but we can turn to the sources of our personal behavior and manipulate them. We will need help. Better organized social networks and the self-management techniques they support can promote immediate changes in consumption at home, work, and moving about in our personal worlds. Surprisingly, consuming less can lead to more satisfying and happier lives, but a better understanding of reinforcement contingencies is necessary. We can recover the strengthening effects of personal daily accomplishments that are eroded when conditioned generalized reinforcers intervene. When we get our own personal lives in order we can reduce our carbon footprints, restore the connections between our behavior and its strengthening effects, and become models worthy of imitation.


Primary Acute Neuromuscular Respiratory Failure.
Neurologists are often called to evaluate patients with both defined and undiagnosed neuromuscular disorders when respiratory failure develops to determine if there is a neuromuscular cause. Being able to confidently diagnose neuromuscular respiratory failure and intervene appropriately is imperative, as early intervention and determination of the cause have survival implications. Outcomes are poor when the cause of neuromuscular weakness and resultant respiratory failure cannot be identified. This review discusses the clinical recognition of primary neuromuscular respiratory failure, its pathophysiology, diagnostic evaluation, and management, focusing on management of respiratory failure in the setting of Guillain-Barré syndrome and myasthenic crisis.


Growth control of activated, synchronized murine B cells by the C3d fragment of human complement.
Three restriction points control the cell cycle of activated B lymphocytes. The first occurs directly after mitosis and is controlled by the occupancy of surface-bound immunoglobulin. The second is observed approximately 4 h after mitosis in the G1 phase of the cycle, that is, before DNA replication, and is controlled by growth factors that are produced by macrophages which we have previously classified as alpha-type factors. The third restriction point occurs in the G2 phase, 2-4 h before mitosis, and is controlled by beta-type growth factors probably produced by helper T lymphocytes. The third component of complement, C3, has long been implicated in the control of B-cell responses. C3 is secreted by monocytes and macrophages. We have found recently that crosslinked, but not soluble, human C3 stimulates activated, but not resting, murine B cells to thymidine uptake. Here we investigate the role of C3b and C3d in the progression of the cell cycle of activated, synchronized murine B cells. We find that crosslinked C3d replaces the action of alpha-factors within the cell cycle of these cells and allows entry into S phase. In contrast, soluble C3d inhibits the action of alpha-factors. This implies that a C3d-specific receptor, probably the murine analogue to the human complement receptor CR2, is a growth factor receptor on activated B cells that will give the cell a growth-positive signal when it is crosslinked, while occupancy by the soluble form of C3d will result in inhibition of the action of alpha-factors or of crosslinked C3b or C3d. A stretch of weak homology between the cDNA sequence of murine C3d and those of murine growth factors indicates that an insulin-like growth factor could be the active principle of C3d that controls the cell cycle of activated B cells.


Single dose bioequivalence study of two brands of olanzapine 10 mg tablets in Iranian healthy volunteers.
This single dose, randomized, open label, 2-period and crossover study in healthy Iranian adult volunteers was conducted to compare the bioavailability of 2 branded formulations of olanzapine 10 mg tablets. 24 volunteers received one tablet of each olanzapine 10 mg formulation. Drugs were administered after a 12 h overnight fast in each of 2 treatment days which separated by a 2-week washout period. Serial blood samples were collected over a period of 72 h. Plasma was analyzed using a validated high performance liquid chromatography method with ultraviolet detection in the range of 2-24 ng/mL with a lower limit of quantitation of 1.25 ng/mL. A non-compartmental method was employed to determine the pharmacokinetic properties (Cmax, Tmax, AUC0-t, AUC0-∞ and T1/2) to test to bioequivalence. Cmax, AUC0-t and AUC0-∞ were used to test the bioequivalence after log-transformation of plasma data. The mean (SD) Cmax, AUC0-t and AUC0-∞ for the test formulation were 15.82 (3.15) ng/mL, 447.19 (100.64) ng.h/L and 570.75 (130.55) ng.h/L respectively. Corresponding values for the test formulation were 15.72 (4.25) ng/mL, 440.37 (98.75) ng.h/mL and 558.66 (129.57) ng.h/mL. For test formulation vs. the reference formulation, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t and AUC0-∞ were 97.6-110.0%, 96.4-109.4% and 97.3-109.2%. In these volunteers, based on the FDA regulatory definition, results from the pharmacokinetic analysis suggested that the test and reference formulations of olanzapine 10 mg tablets were bioequivalent.


[Surgery of burn sequelae on the scalp].
Surgical treatment of scalp burn sequelae has achieved a decisive step with the use of tissue expansion. First, authors propose a brief recap on anatomy, physiopathology and usual surgical processes. Then they describe in details the tissue expansion and present some experimental results. As a conclusion, they discuss the learning curve associated with such a process.


Microsurgical treatment of intracranial aneurysms.
An important advance in aneurysm surgery is the operating microscope, which allows the neurosurgeon access to previously inoperable lesions. The authors describe the technique and document their results in 19 aneurysms.


Identification of inhibitors of α2β1 integrin, members of C-lectin type proteins, in Echis sochureki venom.
Snake venom antagonists of α2β1 integrin have been identified as members of a C-lectin type family of proteins (CLP). In the present study, we characterized three new CLPs isolated from Echis sochureki venom, which interact with this integrin. These proteins were purified using a combination of gel filtration, ion exchange chromatography and reverse phase HPLC. Sochicetin-A and sochicetin-B potently inhibited adhesion of cells expressing α2β1 integrin and binding of isolated α2β1 ectodomain to collagen I, as well as bound to recombinant GST-α2A domain in ELISA, whereas activity of sochicetin-C in these assays was approximately two orders of magnitude lower. Structurally, sochicetin-B and sochicetin-C are typical heterodimeric αβ CLPs, whereas sochicetin-A exhibits a trimer of its subunits (αβ)₃ in the quaternary structure. Immobilized sochicetins supported adhesion of glioma cell lines, LN18 and LBC3, whereas in a soluble form they partially inhibited adhesion of these cells to collagen I. Glioma cells spread very poorly on sochicetin-A, showing no cytoskeleton rearrangement typical for adhesion to collagen I or fibronectin. Adhesion on CLP does not involve focal adhesion elements, such as vinculin. Sochicetin-A also inhibited collagen-induced platelet aggregation, similar to other CLPs' action on the blood coagulation system.


Distribution coefficients of potentially toxic elements in soils from the eastern Amazon.
The solid-solution distribution or partition coefficient (Kd) is a measure of affinity of potentially toxic elements (PTE) for soil colloids. Kd plays a key role in several models for defining PTE guideline values in soils and for assessing environmental risks, and its value depends on edaphic and climatic conditions of the sites where the soils occur. This study quantified Kd values for Cd, Co, Cr, Cu, Hg, Ni, Pb, and Zn from representative soil samples from Brazil's eastern Amazon region, which measures 1.2 million km(2). The Kd values obtained were lower than those set by both international and Brazilian environmental agencies and were correlated with the pH, Fe and Mn oxide content, and cationic exchange capacity of the soils. The following order of decreasing affinity was observed: Pb>Cu>Hg>Cr>Cd≈Co>Ni>Zn.


Stability and conformational dynamics of metallothioneins from the antarctic fish Notothenia coriiceps and mouse.
The structural properties and the conformational dynamics of antarctic fish Notothenia coriiceps and mouse metallothioneins were studied by Fourier-transform infrared and fluorescence spectroscopy. Infrared data revealed that the secondary structure of the two metallothioneins is similar to that of other metallothioneins, most of which lack periodical secondary structure elements such as alpha-helices and beta-sheets. However, the infrared spectra of the N. coriiceps metallothionein indicated the presence of a band, which for its typical position in the spectrum and for its sensitivity to temperature was assigned to alpha-helices whose content resulted in 5% of the total secondary structure of the protein. The short alpha-helix found in N. coriiceps metallothionein showed an onset of denaturation at 30 degrees C and a T(m) at 48 degrees C. The data suggest that in N. coriiceps metallothionein a particular cysteine is involved in the alpha-helix and in the metal-thiolate complex. Moreover, infrared spectra revealed that both proteins investigated possess a structure largely accessible to the solvent. The time-resolved fluorescence data show that N. coriiceps metallothionein possesses a more flexible structure than mouse metallothionein. The spectroscopic data are discussed in terms of the biological function of the metallothioneins.


A Fluorescence Resonance Energy Transfer Biosensor Based on Graphene Quantum Dots and Protoporphyrin IX for the Detection of Melamine.
Graphene quantum dots (GQDs), which have high photostability, anti-photobleaching and scintillation, good biocompatibility and low toxicity, are important member of the fluorescent material family, and have attracted extensive research interest. In this paper, a fluorescence resonance energy transfer (FRET) biosensor based on protoporphyrin IX (PpIX) and GQDs was developed for melamine detection. PpIX was bound to the surface of GQDs to produce self-assembled nanosensors, and a FRET process occurred between GQDs and PpIX. However, due to the combination of melamine and PpIX, the FRET process was shut down in the presence of melamine. The FRET system could quickly and accurately detect melamine with a detection range of 1.0 × 10-8 to 2.0 × 10-6 mol/L based on the fluorescence intensity ratio of PpIX and GQDs, and the detection limit was 3.6 × 10-9 mol/L. This method obtained satisfactory results when it was employed to the determination of melamine in milk samples.