Effects of grammar complexity on artificial grammar learning.
The present study identified two aspects of complexity that have been manipulated in the implicit learning literature and investigated how they affect implicit and explicit learning of artificial grammars. Ten finite state grammars were used to vary complexity. The results indicated that dependency length is more relevant to the complexity of a structure than is the number of associations that have to be learned. Although implicit learning led to better performance on a grammaticality judgment test than did explicit learning, it was negatively affected by increasing complexity: Performance decreased as there was an increase in the number of previous letters that had to be taken into account to determine whether or not the next letter was a grammatical continuation. In particular, the results suggested that implicit learning of higher order dependencies is hampered by the presence of longer dependencies. Knowledge of first-order dependencies was acquired regardless of complexity and learning mode.


The in vitro effect of estradiol and testosterone on iron-induced lipid peroxidation in rat brain and kidney tissues.
The effects of estradiol and testosterone on iron-induced lipid peroxidation were compared in rat brain and kidney homogenates in vitro. Lipid peroxidation in the form of malondialdehyde (MDA) was evaluated by the measurement of thiobarbituric acid (TBA) reactive substances. Estradiol inhibited lipid peroxidation in both tissues studied in a dose-dependent manner. The effect was five times stronger in brain than in kidney. Testosterone did not affect lipid peroxidation in either tissue. Estradiol-induced inhibition of brain lipid peroxidation might contribute to the neuroprotective effect of estrogens.


Clinical studies on three cases of the interval form of carbon monoxide poisoning: serial proton magnetic resonance spectroscopy as a prognostic predictor.
Three patients with the interval form of carbon monoxide (CO) poisoning were studied for associations between their clinical courses and serial changes on: (1) MRI; (2) EEG; (3) single photon emission computed tomography with N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP SPECT); and (4) proton magnetic resonance spectroscopy ([1HIMRS) to evaluate their usefulness as prognostic predictors. A hyperintense area on MRI T2-weighted images and a hypointense area on T1-weighted images, appearing in the deep white matter, persisted for a prolonged period even after improvement of the clinical symptoms, and did not become an accurate indicator of clinical evaluation or prognosis. [1H]MRS studies with the volume of interest set in the frontal lobe white matter revealed increases in choline-containing compounds, and reductions of N-acetylaspartate in all cases. These findings normalized in one subclinical case over time. Distinctive findings in the severe cases included increased lactate in two cases showing akinetic mutism, with a difference in prognosis noted according to the degree and period of persistence of this increase. EEG findings were relatively well correlated with clinical symptoms in the early period, with a good correlation no longer consistent after a certain period was exceeded. [123I]IMP SPECT findings did not always reflectclinical symptomatology either. These results indicate that [1H]MRS is the most useful indicator in the clinical evaluation of patients with the interval form of CO poisoning.


Bone mineralization in newborns whose mothers received magnesium sulphate for tocolysis of premature labour.
Prolonged maternal magnesium sulphate infusion therapy for tocolysis of premature labour may result in secondary fetal hypermagnesaemia, which has been associated with bony abnormalities in the newborn. We report on four infants, members of two twin pregnancies, who were exposed to prolonged fetal hypermagnesaemia. Three of the infants, all appropriate for gestational age, showed abnormal radiological findings consisting of abnormal mineralisation of long-bone metaphyses owing to fetal hypermagnesaemia. The fourth infant, who was growth retarded, had normal bones. Intrauterine growth restriction appears to be protective against magnesium sulphate-induced abnormal bone mineralisation in the newborn.


Cross-sectional study for the clinical application of extracorporeal membrane oxygenation in Mainland China, 2018.
To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018. Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database. The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31-63), and 1346 were male. The average hospital stay was 17 days (IQR 7-30), and the average costs per case was $36,334 (IQR 22,547-56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality. Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.


T cell clones specific for hybrid I-A molecules. Discrimination with monoclonal anti-I-Ak antibodies.
Alloreactive and soluble antigen-reactive, I-A-restricted T cell clones were examined for their ability to recognize hybrid I-A antigens. Several clones that recognized hybrid I-A(b)/I-A(k) molecules on (C57BL/6 x A/J)F(1) [(B6A)F(1)] spleen cells were studied. We were able to distinguish clones that recognized hybrid I-A molecules of the A(b)(a)A(k)(beta) type from those that recognized A(k)(a)A(b)(beta) molecules. We reached this conclusion by considering data from three independent types of experiments. (a) Monoclonal antibodies were used to inhibit T cell stimulation. Antibodies 10.2.16 and H116.32 distinguished two mutually exclusive "families" of T cell clones. One group of clones was inhibited by 10-2.16 and not H116.32, the other group exhibited reciprocal inhibition. (b) T cell proliferation was assayed using antigen-presenting cells from B6.C-H-2(bml2) (bml2) and [bml2 x B10.A(4R)]F(1) mice. Because the bml2 strain has a mutation that results in an altered A(b)(beta) polypeptide chain (A(bm12)(beta)), we reasoned that clones that could recognize the [bm12 x B 10.A(4R)]F(1) cells were recognizing A(b)(a)A(k)(beta) molecules. Alternatively, clones not recognizing [bml2 x B10.A(4R)]F(1) cells had specificity for A(k)(a)A(b)(beta) molecules. (c) I-A molecules immunoprecipitated from radiolabeled (B6A)F(1) splenocyte extracts were analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These experiments confirmed an earlier report that antibody 10.2.16 recognized determinants on the A(k)(beta) chain (12). Antibody H116.32 immunoprecipitated products consistent with recognition of A(k)(a) determinants. Taken together, these three types of results offer conclusive evidence that T cell clones recognizing "hybrid" I-A molecules use either A(b(k)A(k)(beta) or A(k)(a)A(b)(beta) molecules as recognition or restriction sites. Clones whose proliferation was supported by [bm 12 x B10.A(4R)]F(1) cells and blocked by anti-I-A(k) antibody 10-2.16 recognized A(b)(a)A(k)(beta) B molecules. Clones that were blocked by antibody H116.32 and did not recognize [bml2 X B10.A(4R)]F(1) cells use a recognition site(s) on A(b)(a)A(k)(beta) molecules. Thus, we can demonstrate both functionally and biochemically that hybrid F(1) I-A molecules of the structure A(k)(a)A(b)(beta) and A(b)(a)A(k)(beta) both exist on (B6A)F(1) splenocytes and that both configurations are used in immune recognition phenomena.


Multiple long-term conditions within households and use of health and social care: a retrospective cohort study.
The daily management of long-term conditions falls primarily on individuals and informal carers, but the impact of household context on health and social care activity among people with multiple long-term conditions (MLTCs) is understudied. To test whether co-residence with a person with MLTCs (compared with a co-resident without MLTCs) is associated with utilisation and cost of primary, community, secondary health care, and formal social care. Linked data from health providers and local government in Barking and Dagenham for a retrospective cohort of people aged ≥50 years in two-person households in 2016-2018. Two-part regression models were applied to estimate annualised use and cost of hospital, primary, community, mental health, and social care by MLTC status of individuals and co-residents, adjusted for age, sex, and deprivation. Applicability at the national level was tested using the Clinical Practice Research Datalink (CPRD). Forty-eight per cent of people with MLTCs in two-person households were co-resident with another person with MLTCs. They were 1.14 (95% confidence interval [CI] = 1.00 to 1.30) times as likely to have community care activity and 1.24 (95% CI = 0.99 to 1.54) times as likely to have mental health care activity compared with those co-resident with a healthy person. They had more primary care visits (8.5 [95% CI = 8.2 to 8.8] versus 7.9 [95% CI = 7.7 to 8.2]) and higher primary care costs. Outpatient care and elective admissions did not differ. Findings in national data were similar. Care utilisation for people with MLTCs varies by household context. There may be potential for connecting health and community service input across household members.


The electrocardiographic and clinical diagnosis of myocardial contusion.
The clinical features and treatment of 34 patients with myocardial contusion is presented. The value of specific clinical features for diagnosis is discussed. Guidlines for therapy are presented.


Recent preparation, modification and application progress of starch nanocrystals: A review.
Due to the advantages of wide sources, high biocompatibility and favorable biodegradability, starch nanocrystals (SNCs) have gradually attracted attention and have bright development prospects in food, agriculture, materials, medicine and other fields. However, the traditional preparation method of SNCs is time-consuming and inefficient, and the physicochemical properties cannot fully meet the needs of multiple applications. Fortunately, the unique onion-like structure of starch granules and the large number of hydroxyl groups present on the surface entitle SNCs to efficient preparation and modification. This paper comprehensively reviewed the improvement methods of SNCs preparation process in recent years, and the advantages and disadvantages of the two improvement strategies were compared. Besides, the importance of introducing different pretreatment methods into the SNCs preparation process was emphasized. It also focused on the different modification treatment and application progress of SNCs, especially in the starch-based surface coating of fruits and vegetables. The information will contribute to further improve the preparation efficiency and physicochemical properties of SNCs, and ultimately expand the application field.


Tunable long persistent luminescence in the second near-infrared window via crystal field control.
Construction of an active composite as a biomarker with deeper tissue penetration and higher signal-to-noise ratio (SNR) is of great importance for the application in bioimaging. Here, we report a strategy for tuning the emission bandwidth and intensity via crystal field control in long persistent phosphors (LPPs). Ni2+-doped Zn1+ySnyGa2-x-2yO4 phosphors, with a tunable emission band peaking from 1270 to 1430 nm in the second near-infrared (NIR) window, have been successfully prepared. Such featured materials have the advantages of low absorption and scattering as well as more efficient tissue penetration. The emission spectra can be controlled by tailoring the local crystal field around the activator precisely via substitution of Zn and Sn for Ga. Moreover, with high resolution and weak light disturbance, these developed multi-band afterglow phosphors exhibit great application potential in advanced optical imaging.


Placebo effect in subjects with cognitive impairment.
Understanding both the placebo response and the underlying disease progression is crucial to designing clinical trials and interpreting results in Alzheimer's disease (AD) research. The disease severity at different stage of disease (e.g., mild cognitive impairment (MCI), early or late AD) is related to the rate of disease progression, which make it even difficult for AD researchers to understand the clinical trial results. A model-based meta-analysis approach using all available historical data provides quantitative understanding of placebo effect and disease progression in AD and offers a useful tool to aid in both trial design and trial interpretation. The Critical Path Institute (C-Path) is a nonprofit organization founded in 2005 as a vehicle to develop tools to accelerate drug development. The drug development tool (DDT) with AD is the first-ever quantitative DDT to be endorsed by FDA and EMA, and is publicly available to researchers through C-Path's website: https://c-path.org/ad-cts-tool-request/.


Efficacy and Safety of Gamma Ventral Capsulotomy for Treatment-Resistant Obsessive-Compulsive Disorder: A Single-Center Experience.
Obsessive-compulsive disorder (OCD) is a chronic disease with a lifetime prevalence of 3% and is associated with severe impairment in familial and socio-occupational functioning. Gamma ventral capsulotomy (GVC) is a treatment choice in carefully chosen patients, with few published reports. In this study, we aimed to report the efficacy and safety of GVC in 21 patients with treatment-resistant OCD. This is a retrospective single-center study. Twenty-one patients meeting the selection criteria were included. Patients were considered responders if there were ≥35% reduction in post-GVC Yale-Brown Obsessive Compulsive Scale scores and considered in remission if scores were ≤8. The mean and median clinical follow-up durations were 60.7 and 56 months, respectively (range, 38-149 months). The mean baseline Yale-Brown Obsessive Compulsive Scale score of 35.7 (n = 21) decreased to 15.3 (n = 20) at 36 months follow-up evaluation (P < 0.0001). Fifteen patients (75%) achieved a full response. Of those patients, 7 (35%) were considered to be in remission. There were no partial responders, and 5 patients (25%) were classified as nonresponders. The pre-GVC mean Beck Depression Inventory-II score of 35.1 (n = 21) decreased to 13.8 (n = 20) at 36 months follow-up evaluation (P < 0.0001). Three patients (14.3%) had a transient post-GVC headache that resolved within a week, and 2 patients (9.5%) had persistent headaches that responded to 2-week oral corticosteroid treatment. A brain cyst developed after GVC in 2 patients (10%). No clinically notable abnormalities were seen on neurologic examination at any follow-up. Gamma ventral capsulotomy is a reasonable treatment method in select patients with treatment-resistant OCD.


A new rapid and simple method to determine the kinetics of electrode reactions of biologically relevant compounds from the half-peak width of the square-wave voltammograms.
A new method is introduced to determine the kinetic parameters of electron transfer reactions of biologically important compounds, based on the measurements of the half-peak width (DeltaE(p/2)) of the square-wave voltammograms. A simple surface (diffusionless) redox reaction, and a simple electrode reaction occurring from dissolved state are considered as model systems. In the region of quasireversible electron transfer, the half-peak widths of theoretical square-wave voltammograms are linear functions of the logarithm of the dimensionless kinetic parameter ln(K) that characterizes the rate of the electron transfer reaction. The dimensionless kinetic parameter K is defined as K=k(s)(fD)(-0.5) for the redox reaction taking place from dissolved state, whereas for the surface redox reaction K is defined as K=k(s)/f (k(s) is the standard rate constant of electron transfer, f is the SW frequency, and D is the diffusion coefficient). A set of linear regression equations for the dependences DeltaE(p/2)vs. ln(K) are derived, which can be used for rapid and precise determination of the charge-transfer kinetic parameters. The estimated values for the standard rate constants of various biologically relevant redox systems using this approach are in very good agreement with the experimental values determined by other square-wave voltammetric methods. The square-wave voltammetric half-peak width method can be used as a simple and reliable alternative to other voltammetric methods developed for the kinetic characterization of electron transfer rates.


[Data processing and blood transfusion activities: fact and future in 2013].
It is now hard to think of blood transfusion activities without data processing. Blood transfusion centers are unable to work without it since a long time. Its necessity in hospital blood banks is following the same pattern. Electronic data interchange between them is growing because of their high interdependence. A lot has already been done and works routinely. But a lot remains to be done, due to continuous evolution of computer science and blood transfusion itself.


Preparations for the Assessment of COVID-19 Infection and Long-Term Cardiovascular Risk.
Studies showing that coronavirus disease 2019 (COVID-19) is associated with an increased risk of cardiovascular disease continue to be published. However, studies on how long the overall cardiovascular risk increases after COVID-19 and the magnitude of its long-term effects have only been confirmed recently. This is partly because the distinction between cardiovascular risk as an acute complication of COVID-19 or post-acute cardiovascular manifestations is ambiguous. Long-COVID has arisen as an important topic in the second half of the pandemic. This term indicates that symptoms persist for more than two 2 months; following three months of SARS-CoV-2 infection and cannot be explained by other medical conditions. Despite the agreement of these international organizations and experts, it is difficult to define whether there is sufficient medical evidence to prove the existence of long-COVID. However, the Korean government and Korea Disease Control and Prevention Agency (KDCA) are preparing a new platform to assess the long-term impact of COVID-19. Using this data, a prospective cohort of 10,000 confirmed COVID-19 cases will be established. This cohort will be linked with claims data from the National Health Insurance Services (NHIS) and it is expected that increased real-world evidence of long-COVID will be accumulated.


Improving detection by pediatric residents of endotracheal tube dislodgement with capnography: a randomized controlled trial.
The authors sought to determine if capnography could improve time to correction of a simulated endotracheal tube (ETT) dislodgement by pediatric residents. Pediatric residents attended a didactic session that included interpretation of capnography. A randomized controlled study was then performed using patient simulators. Residents were randomized to standard monitoring (control group) or standard monitoring plus capnography (intervention group). The primary outcome was time to correction of ETT dislodgement. Correction of dislodgement prior to decline in pulse oximetry was our secondary outcome. Twenty-seven subjects completed the simulation. Subjects in the intervention group corrected the ETT dislodgement faster than those in the control group (2.38 minutes vs 3.92 minutes, P = .02). There were no differences in time to correction based on postgraduate year, clinical experiences, or comfort with capnography. Two subjects corrected the dislodgement prior to changes in pulse oximetry, both from the intervention group. Fifty-nine percent of subjects had seen capnography used in the past and 82% felt very or somewhat comfortable with capnography. Capnography decreased time to correction of ETT dislodgement by pediatric residents. Capnography should be considered as an essential monitoring device for intubated patients to enhance patient safety.


The protein coats or ghosts of coliphage T2. I. Preparation, assay, and some chemical properties.
A method of preparing the protein coats or ghosts of phage T2 is described along with proof that the lytic action is a property of the ghost. An assay based on the lytic action toward host cells has been developed which permits a rapid evaluation of the number of ghosts with a reliability of +/-15 per cent. The antigenic and certain physicochemical properties of the ghost have been determined.


Mixed tocopherols have a stronger inhibitory effect on lipid peroxidation than alpha-tocopherol alone.
Intake of vitamin E with food (mixed tocopherols) has been found to counteract the development of atherosclerotic cardiovascular disease, whereas intake of large amounts of pure alpha-tocopherol has shown only a slight or no effect in clinical studies. This study was designed to investigate the effects of alpha-tocopherol alone and a mixed tocopherol preparation (gamma-, delta-, and alpha-tocopherol) on hydrogen peroxide-induced lipid peroxidation in human erythrocytes. Erythrocytes were incubated with different concentrations of alpha-tocopherol or mixed tocopherols and then exposed to hydrogen peroxide. Tocopherol levels and malondialdehyde-thiobarbituric acid-reactive substances were determined by high-performance liquid chromatography and fatty acids by gas chromatography. Incubation of erythrocytes with tocopherols (30-120 microM) increased the tocopherol level in a concentration-dependent manner. The uptake of gamma- and delta-tocopherols was much higher than that of alpha-tocopherol. Hydrogen peroxide strongly increased lipid peroxidation and decreased polyunsaturated fatty acids in erythrocytes. Both alpha-tocopherol and the tocopherol mixture protected the cells from lipid peroxidation, the mixture being much more potent than alpha-tocopherol alone. This study indicates that a mixture of tocopherols has a stronger inhibitory effect on lipid peroxidation induced in human erythrocytes than alpha-tocopherol alone, due to higher uptake of gamma- and delta-tocopherol in the cells.


Riparian vegetation model to predict seedling recruitment and restoration alternatives.
Native riparian vegetation communities have declined downstream of large water infrastructure like dams and diversions, owing to water management operations that prevent successful seedling colonization and recruitment. Altered timing and magnitude of reservoir releases to fulfill competing water demands often lead to reduced peak discharges and flow recession rates that do not support native riparian reproduction processes. To achieve short-term ecosystem function in highly regulated rivers an alternative method might be restoration planting, whereby success depends on identifying appropriate planting location and spatial extents. This study aims to provide a methodology to inform resource managers about the extent of possible natural seedling recruitment under average and wet hydrologic conditions, as well as constrain restoration planting operational uncertainties. Results from field surveys and simulations showed limited favorable areas for successful riparian seedling recruitment under regulated flows, regardless of hydrologic conditions in the basin. However, wet (11.4 ha) hydrologic conditions were more (approximately 11 times) favorable than average (1 ha) conditions for seedling recruitment. Furthermore, model results identified the location and spatial extent (25.6 ha) of favorable restoration planting areas during average flow. This extent is approximately 25 times larger than natural recruitment during an average (hydrological) year and even twice that for natural recruitment for a wet year. This suggests that ground operational activities guided by numerical modeling may effectively constrain planting uncertainties.


Retracted: Influencing Factors and Improvement Path of Synergistic Value Creation Efficiency of Emerging Enterprises.
[This retracts the article DOI: 10.1155/2022/8075349.].


Machine Learning for In Silico ADMET Prediction.
ADMET (absorption, distribution, metabolism, excretion, and toxicity) describes a drug molecule's pharmacokinetics and pharmacodynamics properties. ADMET profile of a bioactive compound can impact its efficacy and safety. Moreover, efficacy and safety are considered some of the major causes of clinical attrition in the development of new chemical entities. In past decades, various machine learning or quantitative structure-activity relationship (QSAR) methods have been successfully integrated in the modeling of ADMET. Recent advances have been made in the collection of data and the development of various in silico methods to assess and predict ADMET of bioactive compounds in the early stages of drug discovery and development process.


The Development of Dental Informatics of Oral Cancer Screening for Prevention in Community Level: A Prototype Study in Thailand.
The purpose of this study is to identify general dentists' information needs for oral cancer screening in community and the information sources they use to meet those needs in clinical settings so as to inform the design of dental information systems. A semi-structured interview was conducted with a convenience sample of 8 general dentists and 5 dental assistant in the Public Health Region 9 area during clinical hours. One hundred and five patient cases were reported by these dentists. Interview transcripts were coded and analyzed using thematic analysis with a constant comparative method to identify categories and themes regarding information needs and information source use patterns. Two top-level categories of information needs were identified: foreground and background information needs. To meet these needs, dentists used four types of information sources: clinical information/tasks, risk factor of oral cancer in general people, surveillance in community and referral to oral cancer treatment. Major themes of dentists' unmet information needs include: (1) timely access to information on various subjects; (2) better visual representations of dental problems; (3) access to patient-specific evidence-based information; and (4) accurate, complete and consistent documentation of patient records. Resource use patterns include: (1) dentists information needs matched information source use; (2) little use of electronic sources took place during treatment; (3) source use depended on the nature and complexity of the dental problems; and (4) dentists and dental nurse routinely practiced cross-referencing to verify patient information. Dentists have various information needs of oral cancer at the point of care. For future development of dental information or clinical decision support systems, developers should consider integrating high-quality, up-to-date clinical evidence into comprehensive and easily accessible EDRs as well as supporting dentists' resource use patterns as identified in the study.


Peripheral tetra-cationic Pt(II) porphyrins photo-inactivating rapidly growing mycobacteria: First application in mycobacteriology.
In this manuscript, we report, for the first time, the photoinactivation evaluation of tetra-cationic porphyrins with peripheral Pt (II)-bpy complexes in the photodynamic inactivation (PDI) of rapidly growing mycobacterial strains (RGM). Two different isomeric Pt (II)-porphyrins were synthetized and applied. PDI experiments in the strains of Mycobacteroides abscessus subsp. Abscessus (ATCC 19977), Mycolicibacterium fortuitum (ATCC 6841), Mycobacteroides abscessus subsp. Massiliense (ATCC 48898), and Mycolicibacterium smegmatis (ATCC 700084) conducted with adequate concentration (without aggregation) of photosensitizers (PS) under white-light illumination for 90 min showed that the most effective PS significantly reduced the concentration of viable mycobacteria. The present results show that positively charged porphyrins at the meta position (3-PtTPyP) are more efficient PS against M. abscessus, M. fortuitum, M. massiliense, and M. smegmatis. The effectiveness of the molecule as PS for PDI studies is also clear with mycobacteria, which is strongly related with the porphyrin peripheral charge and coordination platinum (II) compounds and consequently their solubility in physiological media. Tetra-cationic PS may be promising anti-mycobacterial PDI agents with potential applications in medical clinical cases and bioremediation.


Self-reported outcome after diode laser hair removal.
Laser-assisted photoepilation has become the procedure of choice for permanent hair reduction. Our purpose was to evaluate patient satisfaction with the procedure using a diode-laser system. A self-administered survey was mailed to 220 patients who underwent treatment between 2000 and 2004. These questions addressed the area treated, number of treatments received, postprocedure hair density, and overall satisfaction. Of 220 patients, 114 (52%) completed the survey. Eighty percent of patients were either "very satisfied" or "somewhat satisfied." Forty percent of patients felt they achieved 75% hair reduction and 38% reported 50% hair reduction. The majority of patients required 5-6 treatments over 13-18 months for maximum improvement. Multiple treatments over this prolonged time were a significant deterrent to treatment completion. The majority of patients (91%) experienced no long-term side effects. Diode-laser hair removal is a safe, well-tolerated procedure. Our patient satisfaction is comparable to hair-count studies in the literature.


Implementation of an Antibiotic Stewardship Initiative in a Large Urgent Care Network.
Urgent Care (UC) encounters result in more inappropriate antibiotic prescriptions than other outpatient setting. Few stewardship interventions have focused on UC. To evaluate the effectiveness of an antibiotic stewardship initiative to reduce antibiotic prescribing for respiratory conditions in a UC network. This quality improvement study conducted in a UC network with 38 UC clinics and 1 telemedicine clinic included 493 724 total UC encounters. The study compared the antibiotic prescribing rates of all UC clinicians who encountered respiratory conditions for a 12-month baseline period (July 1, 2018, through June 30, 2019) with an intervention period (July 1, 2019, through June 30, 2020). A sustainability period (July 1, 2020, through June 30, 2021) was added post hoc. Stewardship interventions included (1) education for clinicians and patients, (2) electronic health record (EHR) tools, (3) a transparent clinician benchmarking dashboard, and (4) media. Occurring independently but concurrent with the interventions, a stewardship measure was introduced by UC leadership into the quality measures, including a financial incentive. The primary outcome was the percentage of UC encounters with an antibiotic prescription for a respiratory condition. Secondary outcomes included antibiotic prescribing when antibiotics were not indicated (tier 3 encounters) and first-line antibiotics for acute otitis media, sinusitis, and pharyngitis. Interrupted time series with binomial generalized estimating equations were used to compare periods. The baseline period included 207 047 UC encounters for respiratory conditions (56.8% female; mean [SD] age, 30.0 [21.4] years; 92.0% White race); the intervention period included 183 893 UC encounters (56.4% female; mean [SD] age, 30.7 [20.8] years; 91.2% White race). Antibiotic prescribing for respiratory conditions decreased from 47.8% (baseline) to 33.3% (intervention). During the initial intervention month, a 22% reduction in antibiotic prescribing occurred (odds ratio [OR], 0.78; 95% CI, 0.71-0.86). Antibiotic prescriptions decreased by 5% monthly during the intervention (OR, 0.95; 95% CI, 0.94-0.96). Antibiotic prescribing for tier 3 encounters decreased by 47% (OR, 0.53; 95% CI, 0.44-63), and first-line antibiotic prescriptions increased by 18% (OR, 1.18; 95% CI, 1.09-1.29) during the initial intervention month. Antibiotic prescriptions for tier 3 encounters decreased by an additional 4% each month (OR, 0.96; 95% CI, 0.94-0.98), whereas first-line antibiotic prescriptions did not change (OR, 1.00; 95% CI, 0.99-1.01). Antibiotic prescribing for respiratory conditions remained stable in the sustainability period. The findings of this quality improvement study indicated that a UC antibiotic stewardship initiative was associated with decreased antibiotic prescribing for respiratory conditions. This study provides a model for UC antibiotic stewardship.


Binuclear ion containing nitrogen as a bridging group.
A binuclear ion ([NH(3))5RuN(2)Ru(NH(3))(5)](5)+ is formed by the direct reaction of N(2) with an aqueous solution of (NH(3))(5)RuOH(2)(2+) at room temperature. The binuclear ion is also formed by the reversible reaction of (NH(3))5RuOH(2)(2+) with (NH(3))(5)RuN(2)(2+). Solid [(NH(3))(5)RuN(2)Ru(NH(3))(5)] (BF(4))(4) has been prepared, and its ultraviolet and infrared spectra are reported.


A psychoeducational intervention increases use of a delirium protocol by Neurologists and Neurosurgeons in patients with brain disorders.
Over 50% of inpatients with neurological disorders may present with a co-morbid psychiatric illness. Delirium has a reported point prevalence of 20% in hospital inpatients and is frequently undetected. We aimed to (1) examine inpatient referrals to a Liaison Neuropsychiatry service and (2) review the diagnosis and management of delirium before and after an educational intervention. An initial 6-month audit of referrals to the inpatient Liaison Neuropsychiatry service was conducted in 2018. We then undertook a psychoeducational intervention to raise awareness of the diagnosis and management of delirium. We conducted a re-audit of referrals to the service in 2019. On initial audit, of 84 referrals, the most common referral was for mood (38%; n = 32). Just 4% (n = 3) had a specific delirium query. Following assessment by Neuropsychiatry, organic disorders (43%; n = 32), including delirium (33%; n = 25), were the most common diagnoses. On re-audit, of 86 referrals, mood assessment remained the most common reason for referral (38%; n = 33) and 2% (n = 2) were referred for possible delirium. Organic disorders remained the most common diagnoses (53%; n = 45) including delirium (38%; n = 32). We found a significant increase in the use of the delirium protocol from 12% (n = 3) on initial audit to 47% (n = 15); p < 0.01 on re-audit despite no increase in the number of specific delirium queries. A psychoeducational intervention improves the management of delirium by Neurologists and Neurosurgeons in patients with brain disorders.


Postconditioning by mild hypoxic exposures reduces rat brain injury caused by severe hypoxia.
A potent neuroprotective effect of ischemic postconditioning has previously been described using cerebral artery occlusion but this is not a practical therapeutic option. The present study has been performed to determine whether postconditioning by mild episodes of hypobaric hypoxia (hypoxic postconditioning, HP) can reduce post-hypoxic brain injury in rats. Male Wistar rats were submitted to severe hypobaric hypoxia (180 Torr, 3 h) followed by HP (360 Torr, 2 h, 3 trials spaced at 24 h) starting either 3h (early HP) or 24 h (delayed HP) after severe hypoxia. The structural and functional brain injury was assessed by a complex of histological techniques, behavioral methods, and by testing the functions of the hypothalamic-pituitary-adrenal axis (HPA). It was found that early and delayed HP considerably attenuated post-hypoxic injury, reducing pyknosis, hyperchromatosis, and interstitial brain edema, as well as the rates of neuronal loss in hippocampus and neocortex. Delayed HP produced prominent anxiolytic effect on rat behavior, preventing development of post-hypoxic anxiety. Both modes of HP had beneficial effect on the functioning of HPA, but only delayed HP normalized completely the baseline HPA activity and its reactivity to stress. The results obtained demonstrate that postconditioning by using repetitive episodes of mild hypobaric hypoxia may provide a powerful neuroprotective procedure that can be easily adopted for clinical practice and recommended as a research tool for identification of endogenous mechanisms involved in post-ischemic neuroprotection.


Nitric oxide modulates placental prostanoid production from late pregnant non-insulin-dependent diabetic rat.
Severe reproductive dysfunction has been described in non-insulin-dependent diabetes mellitus (NIDDM), correlated with high glucose levels in the plasma. We have characterized an abnormal prostanoid profile in tissues from NIDDM rats, and a tight correlation between nitric oxide (NO) levels and prostaglandin production. Likewise, we have determined that parturition is delayed in NIDDM rats compared to control animals. In order to characterize the events which precede delayed parturition in NIDDM rats, we evaluate (a) the arachidonic acid (AA) conversion in placental tissue obtained from control (day 21 and 22) and NIDDM (day 21, 22 and 23) late pregnant rats into prostaglandin E2 (PGE2) and F2alpha (PGF2alpha), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), and (b) NO synthase (NOS) activity in control and NIDDM late pregnant animals. Placental arachidonate conversion from control rats into different prostanoids, namely PGE2, PGF2alpha, and TXB2, is higher in day 22 than in day 21, and radioconversion from diabetic rats into PGE2, PGF22, TXB2 and 6-keto-PGF1alpha on day 23 is higher than in day 21 and 22. 6-keto-PGF1alpha is lower and TXB2 is higher in diabetic tissues than in control. Placental AA conversion of control diabetic tissues on the day of delivery is decreased by N(G) monomethyl-L-arginine (LNMMA) (600 mM), a well known NOS inhibitor, while prostanoid production remains unaltered on previous days. NOS activity is higher in control on day 22 when compared to day 21, and in diabetic on day 23 when compared to day 22 of pregnancy. We conclude that elevated NO placental levels are observed in control (day 22) and NIDDM (day 23) rats, and may increase placental prostaglandin production on the day of delivery.


An idiotypic determinant formed by both immunoglobulin constant and variable regions.
Immunoglobulin idiotypes are serologically defined determinants associated with the variable (V) region of antibody molecules (reviewed in refs 1-4). One of the best defined idiotype systems is that borne by the phosphorylcholine (PC)-binding IgA proteins TEPC15 (T15) and HOPC8 (H8). The T15 idiotype, defined by sera raised in A strain mice, or in rabbits, is considered identical to that expressed by the majority of BALB/c anti-PC antibodies. To define the idiotypic determinants (idiotopes) of which the T15 idiotype is comprised, monoclonal anti-T15 antibodies were used here to examine both serum and monoclonal anti-PC antibodies. The latter were found to differ from T15 with respect to the idiotope defined by the monoclonal anti-idiotope antibody, 21A5, in that the '21A5 idiotope' was absent from anti-PC sera; of the monoclonal anti-PC antibodies examined, only those which were both T15+ and of the IgA isotype seemed to express this idiotype fully. This result suggests that not only the V region, but also the constant (C) region, of the immunoglobulin molecule can contribute to the formation of an idiotypic determinant. Isotype-restricted idiotopes may be involved in the regulation of antibody responses of particular classes.


Endothelin-1 stimulates the Na+/H+ and Na+/HCO3- transporters in rabbit renal cortex.
Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor identified to date, raising the strong possibility of its involvement in the pathogenesis of systemic hypertension. Whether ET-1 exerts a direct stimulating effect on sodium reabsorption in the renal proximal convoluted tubule, the dominant locus of sodium reabsorption in the nephron, is currently unknown. Such an effect would suggest yet another mechanism by which ET-1 might mediate systemic hypertension. In studies on membrane vesicles prepared from rabbit renal cortex, we show that ET-1 (10(-8) to 10(-11) M) exerts dose-dependent stimulation of the apical Na+/H+ exchanger and the basolateral Na+/HCO3- cotransporter; preincubation of vesicles with 10(-10) M ET-1 for five minutes enhanced the activity of each transporter by approximately 25%. This stimulation reflected an increase in the Vmax of each transporter but no change in the Km for sodium. The stimulatory effect of ET-1 was blocked in the presence of an ET-1 antiserum. Moreover, the stimulation of the apical Na+/H+ exchanger and the basolateral Na+/HCO3- cotransporter by ET-1 displayed specificity as indicated by the lack of effects on the activities of the apical Na(+)-glucose transporter and the basolateral Na(+)-succinate transporter. The data implicate ET-1 as a novel, direct and specific modulator of sodium reabsorption in the proximal tubule. As such, ET-1 might be a direct determinant of extracellular fluid volume under normal and pathophysiologic circumstances, including hypertensive disorders.


Recidivism in Liver Transplant Recipients With Alcoholic Liver Disease: Analysis of Demographic, Psychosocial, and Histology Features.
Liver transplant for alcoholic liver disease requires identifying potential recipients at risk for recidivism. We sought to identify risk factors for recidivism and survival in recipients of liver transplant with alcoholic liver disease. Demographic, psychosocial, and histology features were evaluated as risk factors toward harmful recidivism in 148 recipients of liver transplant with alcoholic liver disease. Based on the univariate analysis using Cox proportional hazards model, duration of alcohol abstinence 6 months (HR 3.74; P = .011, 95% CI: 1.36-10.3), non-alcohol related criminal history (HR 3.18; P = .032, 95% CI: 1.1-9.15), support from immediate family (HR 0.24; P = .0061, 95% CI: 0.09-0.67), and active smoking at the time of liver transplant (HR 2.74; P = .041, 95% CI: 1-7.53) were identified as significant predictors for recidivism. Older patients had less likelihood of alcohol relapse (HR 0.91; P = .0014, 95% CI: 0.87-0.97) on univariate model. In multivariate model older patients (HR 0.91; P = .004, 95% CI: 0.86-0.97) and patients who have immediate family support (HR 0.27; P = .012, 95% CI: 0.10-0.76) predicated against recidivism. Suggestive features of alcoholic hepatitis on liver explant did not predict recidivism or long-term survival. One-, three-, and five-year patient survival rates estimated by Kaplan-Meier survival model in the recipients that remained abstinent were 95%, 87%, and 80%, compared with 87%, 49%, and 49% for the recipients with recidivism (P = .001). Recidivism is associated with earlier death after liver transplant. Older recipients and patients with immediate family support are less likely to have alcohol relapse, and have better long-term survival.


Potential roles of Alzheimer precursor protein A4 and beta-amyloid in survival and function of aged spinal motor neurons after axonal injury.
To study the potential role of Alzheimer precursor protein A4 (APP) and beta-amyloid (A/beta) on aging motor neuron survival, expression of APP, A/beta, and choline acetyltransferase (ChaT) were investigated in aged rats after either distal axotomy or root avulsion injury. Approximately 45% in number of total aged spinal motor neuron were normally APP-positive. A/beta-positive neurites were observed normally in the spinal ventral horn of aged rats. After distal axotomy, without apparent neurodegeneration such as cell loss and decreased ChaT-immunoreactivity, increased levels of APP expression were observed in the spinal cords of aged rats post-injury. In contrast, after avulsion, expression of APP and A/beta were downregulated in the spinal ventral horn of aged rats, and marked loss of spinal motor neurons and downregulated ChaT expression were observed. Our data indicate that APP and A/beta might play beneficial roles in neuronal survival of aged spinal motor neurons after axonal injury.


Improvements in cognition and associations with measures of aerobic fitness and muscular power following structured exercise.
Cognition, along with aerobic and muscular fitness, declines with age. Although research has shown that resistance and aerobic exercise may improve cognition, no consensus exists supporting the use of one approach over the other. The purpose of this study was to compare the effects of steady-state, moderate-intensity treadmill training (TM) and high-velocity circuit resistance training (HVCRT) on cognition, and to examine its relationships to aerobic fitness and neuromuscular power. Thirty older adults were randomly assigned to one of three groups: HVCRT, TM, or control. Exercise groups attended training 3 days/wk for 12 weeks, following a 2 week adaptation period. The NIH Cognitive Toolbox was used to assess specific components of cognition and provided an overall fluid composite score (FCS). The walking response and inhibition test (WRIT) was specifically used to assess executive function (EF) and provided an accuracy (ACC), reaction time (RT) and global score (GS). Aerobic power (AP) and maximal neuromuscular power (MP) were measured pre- and post-intervention. Relationships between variables using baseline and mean change scores were assessed. Significant increases were seen from baseline in ACC (MD = 14.0, SE = 4.3, p = .01, d = 1.49), GS (MD = 25.6, SE = 8.0, p = .01, d = 1.16), and AP (MD = 1.4, SE = 0.6, p = .046, d = 0.31) for HVCRT. RT showed a trend toward a significant decrease (MD = -0.03, SE = 0.016, p = .068, d = 0.32) for HVCRT. No significant within-group differences were detected for TM or CONT. Significant correlations were seen at baseline between AP and FCS, as well as other cognitive domains; but none were detected among change scores. Although no significant correlation was evident between MP and FCS or GS, there was a trend toward higher MP values being associated with higher FCS and GS scores. Our results support the use of HVCRT over TM for improving cognition in older persons, although the precise mechanisms that underlie this association remain unclear.


Constitutive, long-term production of human interferons by hamster cells containing multiple copies of a cloned interferon gene.
Hybrid plasmids containing the mouse dihydrofolate reductase (dhfr) and a human interferon (either IFN-alpha 5 or IFN-gamma) coding sequence under the control of viral promoters were transfected into dhfr- Chinese hamster ovary (CHO) cells. dhfr+ colonies produced IFN at 10-1000 units X ml-1 X day-1. Clones selected in methotrexate had a 20-50-fold increase in the IFN-alpha 5 and dhfr DNA and mRNA content and secreted IFN at 20,000-100,000 units X ml-1 X day-1. SDS-polyacrylamide gel electrophoresis of partially purified 35S-HuIFN-gamma from CHO cells showed a multiple of labeled bands with a mobility corresponding to 22,400 to 23,400 daltons which was absent in the supernatants of non-transformed CHO cells. The higher apparent molecular weight of human IFN-gamma from CHO cells as compared to that of human IFN-gamma from E. coli (about 18,800) suggests that the former was glycosylated.


Necrotizing fasciitis in neonates.
Necrotizing fasciitis (NF) is a potentially life-threatening infection of soft tissues. It is characterized by rapid spread of inflammation and infection with widespread necrosis of fascia, subcutaneous tissues, and overlying skin. NF is usually reported in adults with preexisting medical conditions or compromised immune system. It is rare in neonates, and the reported mortality is close to 50% in this population. Less than 70 cases of neonatal NF are reported in literature, most in otherwise healthy neonates and usually attributed to omphalitis, mastitis, or postoperative wound infections. We report our experience of nine neonates who developed NF spontaneously (primary NF) and look at the etiology, clinical presentation, microbiology, management, and outcome.


Nonlinear strict distance and similarity measures for intuitionistic fuzzy sets with applications to pattern classification and medical diagnosis.
In this paper, we propose a new type of nonlinear strict distance and similarity measures for intuitionistic fuzzy sets (IFSs). Our proposed methods not only have good properties, but also improve the drawbacks proposed by Mahanta and Panda (Int J Intell Syst 36(2):615-627, 2021) in which, for example, their distance value of [Formula: see text] is always equal to the maximum value 1 for any intuitionistic fuzzy number [Formula: see text]. To resolve these problems in Mahanta and Panda (Int J Intell Syst 36(2):615-627, 2021), we establish a nonlinear parametric distance measure for IFSs and prove that it satisfies the axiomatic definition of strict intuitionistic fuzzy distances and preserves all advantages of distance measures. In particular, our proposed distance measure can effectively distinguish different IFSs with high hesitancy. Meanwhile, we obtain that the dual similarity measure and the induced entropy of our proposed distance measure satisfy the axiomatic definitions of strict intuitionistic fuzzy similarity measure and intuitionistic fuzzy entropy. Finally, we apply our proposed distance and similarity measures to pattern classification, decision making on the choice of a proper antivirus face mask for COVID-19, and medical diagnosis problems, to illustrate the effectiveness of the new methods.


First Report of Rubber Collection Bowls & Plastic and Bamboo Water Containers as the Major Breeding Source of Ae. albopictus with the Indigenous Transmission of Dengue and Chikungunya in Rural Forested Malaria-Endemic Villages of Dhalai District, Tripura, India: The Importance of Molecular Identification.
With the reports of indigenous cases of dengue and chikungunya in the forest-covered rural tribal malaria-endemic villages of Dhalai District, Tripura, India, an exploratory study was undertaken to identify the vector breeding sites. From June 2021 to August 2022, mosquito larvae were collected from both natural and artificial sources in the villages, house premises, and their nearby forested areas outside of the houses. Other than morphological characterisation, Aedes species were confirmed by polymerase chain reaction targeting both nuclear (ITS2) and mitochondrial genes (COI) followed by bidirectional Sanger sequencing. Aedes albopictus was abundantly found in this area in both natural and artificial containers, whereas Ae. aegypti was absent. Among the breeding sources of molecularly confirmed Ae. albopictus species, rubber collection bowls were found to be a breeding source reported for the first time. Plastic and indigenously made bamboo-polythene containers for storing supply water and harvesting rainwater in the villages with a shortage of water were found to be other major breeding sources, which calls for specific vector control strategies. Natural sources like ponds and rainwater collected on Tectona grandis leaves and Colocasia axil were also found to harbour the breeding, along with other commonly found sources like bamboo stumps and tree holes. No artificial containers as a breeding source were found inside the houses. Mixed breeding was observed in many containers with other Aedes and other mosquito species, necessitating molecular identification. We report six haplotypes in this study, among which two are reported for the first time. However, Aedes aegypti was not found in the area. Additionally, rubber collection bowls, ponds, and water containers also showed the presence of Culex quinquefasciatus and Culex vishnui, known JE vectors from this area, and reported JE cases as well. Different Anopheles vector spp. from this known malaria-endemic area were also found, corroborating this area as a hotbed of several vectors and vector-borne diseases. This study, for the first time, reports the breeding sources of Aedes albopictus in the forested areas of Tripura, with rubber collection bowls and large water storage containers as major sources. Also, for the first time, this study reports the molecular characterisation of the Ae. albopictus species of Tripura, elucidating the limitations of morphological identification and highlighting the importance of molecular studies for designing appropriate vector control strategies. The study also reports the co-breeding of JE and malaria vectors for the first time in the area reporting these vector-borne diseases.


DNA-protein crosslinking in normal and solar UV-sensitive ICR 2A frog cell lines exposed to solar UV-radiation.
DNA-protein crosslinks (DPC) were measured following exposure to the solar UV wavelengths produced by a fluorescent sunlamp in ICR 2A frog cells and two solar UV-sensitive mutants derived from this cell line. Approx. 5-7 DPC per 10(10) dalton were induced in these cells by either 150 kJ/m2 of sunlamp UV greater than 315 nm plus photoreactivating light (PRL) or 10 kJ/m2 of sunlamp UV greater than 295 nm. The irradiated cells were then incubated for 0-24 h and the level of DPC measured using alkaline elution. It was found for the ICR 2A cells exposed to sunlamp UV greater than 315 nm that the level of DPC increased about 3-fold during a 2-h postirradiation incubation and then decreased. The mutant cell lines also showed an enhancement in the level of DPC following irradiation, although it was much less pronounced and the levels decreased much more rapidly. In a similar fashion, the level of DPC increased in ICR 2A cells exposed to sunlamp UV greater than 295 nm with more than a 5-fold enhancement after a 4-h incubation. Once again, the mutant cell lines showed an increase in the level of DPC that was smaller and more transient than the effect in the ICR 2A cells. These results suggests that this enhancement in DPC may be indicative of a process that plays a role in cellular survival following solar UV-irradiation.


Macrophages loaded with doxorubicin by ATP-mediated permeabilization: potential carriers for antitumor therapy.
In many cell types extracellular ATP (ATPe) has been shown to cause reversible plasma membrane permeabilization to low molecular weight (< 900 Da) water-soluble compounds. In the present report we have exploited this technique to incorporate the anticancer drug doxorubicin (DXR), molecular mass 543 Da, into the cytoplasm of two mouse cell lines that had previously been shown to express the ATPe-gated pore, J774 macrophages and tumor necrosis factor (TNF)-resistant L929 fibroblasts. Compared to passively loaded cells, ATPe-mediated reversible permeabilization allowed an at least 4-fold increase in DXR intracellular trapping (0.5 pg/cell versus 2 pg/cell). Analysis of the release kinetics at 37 degrees C showed that about 40% of total intracellular DXR was discharged during the first hour from both ATPe-permeabilized and passively loaded cells; about 15% further release was observed upon incubation up to 4 h. DXR release profiles were similar in ATPe-permeabilized and passively loaded cells. ATPe-permeabilized, DXR-loaded (ATPe-DXR) cells strongly inhibited the proliferation of K562 tumor cells. Taken together these results indicate that ATPe-mediated reversible plasma membrane permeabilization can be effectively used to load cells of different histotypes with high concentrations of DXR. This approach could permit to vehicle high doses of anticancer agents by using living cells while reducing systemic toxic effects.


Ultrasound-mediated microbubble destruction enhances gene transfection in pancreatic cancer cells.
The purpose of this study was to determine whether ultrasound exposure combined with microbubble destruction could be used to enhance non-viral gene delivery in human pancreatic carcinoma cells (PANC-1). The study was performed with four experimental groups: Group P, plasmid alone; Group P+M, plasmid and microbubbles; Group P+U, plasmid and ultrasound; Group P+U+M, plasmid with ultrasound and microbubbles. Plasmid DNA encoding enhanced green fluorescent protein (pEGFP) was gently mixed with commercially available ultrasound microbubble contrast agents (SonoVue; Bracco Diagnostics Inc, Milan, Italy) in Group P+M and Group P+U+M. The different combinations of DNA and DNA plus microbubbles were added to cultured PANC-1 cells under different conditions. Transfection efficiency and cell viability were assessed by FACS analysis (Becton Dickinson, San Jose, CA, USA), confocal laser scanning microscopy, and trypan blue staining. The results demonstrated that microbubbles with ultrasound exposure could significantly enhance the reporter gene expression as compared with other groups (Group P+U+M, 21.4%+/-3.16%; Group P, 2.9%+/-0.45%; Group P+M, 3.1%+/-0.51%; Group P+U, 6.1%+/-1.27%; P<0.01). No statistically significant difference was observed in the PANC-1 cell viability between Group P+U+M and other groups (P>0.05). Our in-vitro findings suggest that ultrasound-mediated microbubble destruction has the potential to promote efficient gene transfer into PANC-1 cells without significant cell death. This non-invasive gene transfer method may be a useful tool for safe clinical gene therapy of pancreatic cancer in the future.


Validation of the Arabic Version of the Minnesota Living with Heart Failure Questionnaire.
The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is commonly used to measure quality of life (QOL) in patients with heart failure (HF). We examined the psychometric properties and cultural validity of an Arabic version of the MLHFQ. An observational cross-sectional study was conducted with 210 adult HF outpatients. Patients were interviewed with the Arabic MLHFQ and the Patient Health Questionnaire (PHQ-9). Cronbach's alpha coefficient and confirmatory factor analysis were conducted. Patients with different NYHA classes and HF-hospitalization histories were compared on QOL to test known-group validity. The confirmatory factor analysis yielded 3 factors: physical, emotional, and social. Three items (4, 8, and 15) had low loadings. The overall Cronbach's alpha coefficient was 0.92. There were significant differences in MLHFQ by PHQ-9 categories, NYHA class, and HF-hospitalization history. This Arabic version of MLHFQ is valid and reliable and can be used in Arabic-speaking Lebanese HF populations.


Successful pregnancy outcome in a lung transplant recipient with tacrolimus immunosuppression. A case report.
The use of tacrolimus (FK506, PROGRAF) in pregnant lung transplant recipients has been very rarely reported. A 32-year-old woman, gravida 1, para 0, had previously undergone a unilateral lung transplant secondary to pulmonary fibrosis. Four years later she spontaneously conceived. During pregnancy, she was maintained on an immunosuppressive regimen of tacrolimus and prednisone. Bi-weekly pulmonary function testing remained unchanged until 34 weeks' gestation. At that time, labor was induced due to concern for allograft rejection. A healthy, 2,208-g, female infant was born via an uncomplicated vaginal delivery. Postpartum transbronchial biopsy showed minimal acute cellular rejection. Lung transplant recipients may achieve successful pregnancy outcomes with the use of tacrolimus.


A sensory transducer homologous to the mammalian peripheral-type benzodiazepine receptor regulates photosynthetic membrane complex formation in Rhodobacter sphaeroides 2.4.1.
The Rhodobacter sphaeroides 2.4.1 tryptophan-rich sensory protein gene, tspO (formerly crtK, ORF160) encodes a 17-kDa protein which has an unusually high content of aromatic amino acids in general and of L-tryptophan in particular. The TspO protein was localized to the outer membrane of aerobically grown R. sphaeroides 2.4.1 by use of a polyclonal antibody against the purified protein. This protein is present in severalfold higher levels in photosynthetic as opposed to aerobic grown cells. Although tspO lies within the crt gene cluster, null mutations have an intact carotenoid biosynthetic pathway. In the TSPO1 mutant there was an increased production of carotenoids and bacteriochlorophyll relative to the wild type, particularly when cells were grown aerobically or semiaerobically. When present in trans the tspO gene restored "normal" pigment production to TSPO1. The effect of the tspO gene on pigment production was shown to take place at the level of gene expression. Because the tspO gene product of R. sphaeroides 2.4.1 shows significant sequence homology and similarity to the peripheral-type benzodoazepine receptor from mammalian sources, TspO-specific antibodies when probed against liver and kidney mitochondrial protein showed strong cross-reactivity. The role of TspO in R. sphaeroides 2.4.1 and its relation to photosynthesis gene expression are discussed.


Initiation of a vertical jump: the human body's upward propulsion depends on control of forward equilibrium.
The aim of the study was to understand: (i), how far anticipatory postural adjustments (APA) participate in the sequences of a complex task; (ii), how, in the sagittal plane, horizontal and vertical progressions of the center of gravity (CG) are managed to achieve the prescribed goal. A posturo-kinetics sequence is identified during which forward CG progression is controlled in terms of a center of pressure (CP)-CG interaction. CP shifts and horizontal CG accelerations are correlated in timing and amplitude. There exists a control of whole body progression during the impulse, implying a braking of forwards movement. Vertical and horizontal CG accelerations are inter-dependent, and backward CP shift duration is related to its forward displacement. During the vertical jump initiation, whole body vertical propulsion and forward fall are linked. To increase impulse amplitude, initial whole body disequilibrium is lengthened and forward CG acceleration is greater. APA programming is probably elaborated on the basis of cognitive evaluation of the antero-posterior disturbance.


Post-training memory facilitation blocks extinction but not retroactive interference.
Rats were trained in a step-down inhibitory avoidance task using a 0.2-mA footshock and tested 6 h later. Exposure to a session of extinction (animals placed on the box where they had been trained and left to explore it freely for 100.0 s without footshocks) or to a series of 10 tones presented in another box, in the dark, 2 h after training, hindered retention test performance. The immediate post-training ip administration of epinephrine (5.0 micrograms/kg), ACTH-(1-24) (0.2 microgram/kg), or lysine-vasopressin (10.0 micrograms/kg) facilitated retention test performance and cancelled the effect of extinction, but not the retroactive interference caused by exposure to the tones. These results support the concept that post-training facilitation induced by the hormones is due to a strengthening of the memory trace left by the avoidance task, whereas the retroactive interference caused by the tones occurs independently from that process and is more likely due to the incorporation of postevent information.


Switch/sucrose-non-fermentable (SWI/SNF) complex (SMARCA4, SMARCA2, INI1/SMARCB1)-deficient colorectal carcinomas are strongly associated with microsatellite instability: an incidence study in 4508 colorectal carcinomas.
Loss of expression of mammalian switch/sucrose-non-fermentable (SWI/SNF) [BRG1/BRM-associated factor (BAF)] complex subunits, including SMARCA4, SMARCA2 and INI1/SMARCB1 (termed SWI/SNF complex deficiency), has been reported in colorectal carcinomas (CRCs) but its frequency and clinical significance are uncertain. We performed immunohistochemistry for SMARCA4, SMARCA2 and SMARCB1 on 4508 consecutive resected CRCs. Loss of SMARCA4 expression was found in 13 cases (0.3%), loss of SMARCA2 expression was found in 59 cases (1.3%), and loss of SMARCB1 expression was found in 21 cases (0.4%). Some CRCs showed loss of expression of more than one subunit, so that 84 CRCs (1.7%) were deficient for at least one component. SWI/SNF complex deficiency was associated with higher grade, a right-sided location, mismatch repair deficiency, and BRAF V600E mutation (P < 0.05); 5.8% of mismatch repair-deficient (MMRd) cases and 5.4% of BRAF V600E-mutant cases were SWI/SNF complex-deficient, as compared with 0.9% and 0.4% of mismatch repair-proficient and BRAF-wild-type cases (P < 0.001). Any loss of SMARCB1 expression and global loss of SMARCA2 expression were associated with statistically significant worse overall survival, whereas SMARCA4-deficient cases showed a trend only towards poor overall survival (P = 0.121). In multivariate analysis, any loss of SMARCA4 expression and global loss of SMARCA2 expression were associated with worse survival [odds ratio (OR) 3.33, P = 0.019; and OR 3.39, P < 0.001]. Of particular note, among the subgroup of cases that were MMRd and BRAF V600E-mutated (otherwise considered to be a good prognostic group), loss of SMARCA4 expression was associated with much worse median survival (10.5 months versus 110.9 months; P = 0.003). SWI/SNF complex deficiency is rare in CRC but is enriched in MMRd cases. Identifying these cases has morphological associations and prognostic significance, and in the future may have potential therapeutic implications.


A rare case of ruptured anterior cerebral artery infected aneurysm with angioinvasion secondary to disseminated Nocardia otitidiscaviarum: A case report and literature review.
The cases of ruptured infected aneurysms secondary to disseminated nocardiosis are exceptionally rare. Therefore, there is no guideline for investigation or optimal treatment. A 51-year-old man with immunocompromised status was first presented with pneumonia and cerebral infarction, where the infected aneurysm was ruptured thereafter. Intraoperative findings revealed left anterior cerebral artery thrombosis and occlusion with evidence of angioinvasion along with pus discharge which was later identified with Nocardia otitidiscaviarum. Our case was the first to report on the angioinvasive nature of cerebral nocardiosis, which occurs concurrently with a ruptured infected aneurysm and an unusual presentation that made the diagnosis and treatment challenging. Cerebral nocardiosis may cause ruptured infected aneurysms in patients with risk factors, especially for immunocompromised hosts. Furthermore, Nocardia can present with severe cerebral manifestation due to angioinvasion causing cerebral infarction accompanied by a ruptured infected aneurysm.


Oral administration of Limonin (LM) exerts neuroprotective effects by inhibiting neuron autophagy and microglial activation in 6-OHDA-injected rats.
Parkinson's disease (PD) is a neurodegenerative disorder that occurs most frequently in middle-aged and elderly people. It is characterized by an insidious onset and a complex etiology, and no effective treatment has been developed. The primary characteristic of PD is the degenerative death of midbrain dopaminergic neurons. The excessive autophagy of neurons and hyperactivation of microglia were shown to be involved in the apoptosis of dopaminergic neurons. Limonin (LM), a type of pure natural compound present in grapefruit or citrus fruits (e. g., lemon, orange) has been reported to inhibit apoptosis and inflammation. However, its role and mechanism of action in PD are unclear. In this study, we explored the effect and mechanism of action of LM in PD. In vivo experiments revealed that LM ameliorated 6-OHDA-induced reduced motor activity and PD-related pathological damage in rats. In vitro experiments revealed that LM inhibited the 6-OHDA-induced apoptosis of PC12 cells by inhibiting the excessive autophagy of neurons. In addition, LM inhibited microglial inflammation by activating the AKT/Nrf-2/HO-1 pathway and protected neurons against microglial inflammation-mediated neurotoxicity. In conclusion, the findings of this experiment demonstrated that LM exerted neuroprotective effects by inhibiting neuronal autophagy-mediated apoptosis and microglial activation in 6-OHDA-injected rats, thus indicating that LM can serve as a candidate for PD by targeting neuroinflammation and neuronal autophagy to inhibit neuronal apoptosis.


C/EBP homologous protein promotes Sonic Hedgehog secretion from type II alveolar epithelial cells and activates Hedgehog signaling pathway of fibroblast in pulmonary fibrosis.
Endoplasmic reticulum (ER) stress is involved in the pathological process of pulmonary fibrosis, including IPF. It affects a broad scope of cellular types during pulmonary fibrosis but the role in epithelial-mesenchymal crosstalk has not been fully defined. The present study aimed to investigate the effects of Shh secretion by ER stress-challenged type II alveolar epithelial cells (AECII) on fibroblast and pulmonary fibrosis. Conditioned medium (CM) from tunicamycin (TM)-treated AECII was collected and incubated with fibroblast. Short hairpin RNA (shRNA) was used for RNA interference of C/EBP homologous protein (CHOP). The effects of CHOP and HH signaling were evaluated by TM administration under the background of bleomycin-induced pulmonary fibrosis in mice. Both expression of CHOP and Shh in AECII, and HH signaling in mesenchyme were upregulated in IPF lung. TM-induced Shh secretion from AECII activates HH signaling and promotes pro-fibrotic effects of fibroblast. Interfering CHOP expression reduced ER stress-induced Shh secretion and alleviated pulmonary fibrosis in mice. Our work identified a novel mechanism by which ER stress is involved in pulmonary fibrosis. Inhibition of ER stress or CHOP in epithelial cells alleviated pulmonary fibrosis by suppressing Shh/HH signaling pathway of fibroblasts.


Parallel changes between lipoprotein lipase activating capacity and lipid concentrations in the serum of rats and ferrets during development and dietary manipulation.
1. The lipoprotein lipase activating capacity of serum from 5 to 22 day old rats and male ferrets fed on diets rich in either beef tallow or maize oil was significantly correlated with the triglyceride concentration in the serum. 2. These increases in activating capacity associated with increased serum triglyceride concentrations were similar to those reported for human serum.


Efficacy of interventions to reduce long term opioid treatment for chronic non-cancer pain: systematic review and meta-analysis.
To review interventions to reduce long term opioid treatment in people with chronic non-cancer pain, considering efficacy on dose reduction and discontinuation, pain, function, quality of life, withdrawal symptoms, substance use, and adverse events. Systematic review and meta-analysis of randomised controlled trials and non-randomised studies of interventions. Medline, Embase, PsycINFO, CINAHL, and the Cochrane Library searched from inception to July 2021. Reference lists and previous reviews were also searched and experts were contacted. Original research in English. Case reports and cross sectional studies were excluded. Two authors independently selected studies, extracted data, and used the Cochrane risk-of-bias tools for randomised and non-randomised studies (RoB 2 and ROBINS-I). Authors grouped interventions into five categories (pain self-management, complementary and alternative medicine, pharmacological and biomedical devices and interventions, opioid replacement treatment, and deprescription methods), estimated pooled effects using random effects meta-analytical models, and appraised the certainty of evidence using GRADE (grading of recommendations, assessment, development, and evaluation). Of 166 studies meeting inclusion criteria, 130 (78%) were considered at critical risk of bias and were excluded from the evidence synthesis. Of the 36 included studies, few had comparable treatment arms and sample sizes were generally small. Consequently, the certainty of the evidence was low or very low for more than 90% (41/44) of GRADE outcomes, including for all non-opioid patient outcomes. Despite these limitations, evidence of moderate certainty indicated that interventions to support prescribers' adherence to guidelines increased the likelihood of patients discontinuing opioid treatment (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1), and that these prescriber interventions as well as pain self-management programmes reduced opioid dose more than controls (intervention v control, mean difference -6.8 mg (standard error 1.6) daily oral morphine equivalent, P<0.001; pain programme v control, -14.31 mg daily oral morphine equivalent, 95% confidence interval -21.57 to -7.05). Evidence on the reduction of long term opioid treatment for chronic pain continues to be constrained by poor study methodology. Of particular concern is the lack of evidence relating to possible harms. Agreed standards for designing and reporting studies on the reduction of opioid treatment are urgently needed. PROSPERO CRD42020140943.


A new species of Ergasilus Nordmann, 1832 (Copepoda: Cyclopoida: Ergasilidae) from Bryconops giacopinii Fernández-Yépez (Characidae) in the Vichada River Basin, Colombia.
A new copepod species, Ergasilus curticrus n. sp. is described based on 14 female specimens collected from the gills of the characid teleost Bryconops giacopinii Fernández-Yépez, captured in the Vichada River Basin in Colombia. The new species has a unique combination of characters including: (i) 2-segmented endopods in legs 1 and 4; (ii) a semi-pinnate, falciform seta on the terminal segment of the first leg exopod; (iii) a 1-segmented fourth leg exopod; (iv) a reduced fifth leg with a single seta; and (v) a circular structure fused to a groove near the lateral margins of the second pedigerous tergite. Only two other known congeners have a 1-segmented leg 4 exopod, E. coatiarus Araujo & Varella, 1998 and E. iheringi Tidd, 1942. Among other characters, they differ from the new species by the lack of a semi-pinnate, falciform seta on the terminal exopodal segment of leg 1 and in the structure and armature of the fifth leg. The prevalence of E. curticrus n. sp. was 13.6% and its mean abundance was 0.4 specimens per host. This is the first new species of Ergasilus Nordmann, 1832 described from the Orinoco River Basin.


Out-of-pocket payments in the Austrian healthcare system - a distributional analysis.
Out-of-pocket spending is an important source of healthcare financing even in countries with established prepaid financing of healthcare. However, out-of-pocket payments (OOPP) may have undesirable effects from an equity perspective. In this study, we analyse the distributive effects of OOPP in Austria based on cross-sectional information from the Austrian Household Budget Survey 2009/10. We combine evidence from disaggregated measures (concentration curve and Lorenz curve) and summary indices (Gini coefficient, Kakwani index, and Reynolds-Smolensky index) to demonstrate the distributive effects of total OOPP and their subcomponents. Thereby, we use different specifications of household ability to pay. We follow the Aronson-Johnson-Lampert approach and split the distributive effect into its three components: progressivity, horizontal equity, and reranking. OOPP in Austria have regressive effects on income distribution. These regressive effects are especially pronounced for the OOPP category prescription fees and over-the-counter pharmaceuticals. Disaggregated evidence shows that the effects differ between income groups. The decomposition analysis reveals a high degree of reranking and horizontal inequity for total OOPP, and particularly, for therapeutic aids and physician services. The results - especially those for prescription fees and therapeutic aids - are of high relevance for the recent and on-going discussion on the reform of benefit catalogues and cost-sharing schemes in the public health insurance system in Austria.


Digitoxin promotes apoptosis and inhibits proliferation and migration by reducing HIF-1α and STAT3 in KRAS mutant human colon cancer cells.
Colon cancer patients with mutant KRAS are resistant to cetuximab, an antibody directed against the epidermal growth factor receptor. New treatment options are needed to improve survival in patients with KRAS mutated colorectal cancer. Digitoxin is a cardiotonic drug, which has been demonstrated to exhibit anticancer effects in a number of cancers. However, the anticancer mechanisms of digitoxin in KRAS mutant human colon cancer cells remain elusive. Our result demonstrated that digitoxin but not cetuximab markedly decreased the expression of hypoxia-inducible factor-1α (HIF-1α), signal transducer and activator of transcription 3 (STAT3) and p-STAT3 protein in KRAS mutant colon cancer cells. Further analysis revealed that digitoxin inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. The phosphorylation levels of ribosomal protein S6 kinase (p70S6K) and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by digitoxin. Digitoxin inhibited the expression and activation of STAT3 through upregulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN), SHP1 and protein inhibitors of activated STAT3 (PIAS3) and direct binding to STAT3. Meanwhile, digitoxin inhibited HIF-1α in STAT3-independent manner in KRAS mutant colon cancer cells. Moreover, digitoxin promoted apoptosis and inhibited proliferation and migration, which was potentially mediated by suppression of HIF-1α and STAT3. We also found that digitoxin administration inhibited tumor growth in a mouse xenograft model. Taken together, our findings highlight the therapeutic potential of digitoxin for the treatment of cetuximab-resistant human colon cancer.


Lone aortic regurgitation, sacroiliitis, and HLA B27. Case history and frequency of association.
An account of aortic regurgitation complicating ankylosing spondylitis is given. Twenty patients with lone aortic regurgitation and without overt spondylitis were examined clinically and radiologically and tissue typed. No evidence of sacroiliitis could be found in any patient. HLA B27 was absent from this group, and no significant disturbance in antigen frequency was noted.


Surgical treatment of arteriovenous angiomas localised in the corpus callosum, basal ganglia and near the brain stem.
Seven cases of deep angiomas, in regions near the midline, were operated on in the National Institute of Neurosurgery, Budapest. In four cases the malformation was not so circumscribed that it could be localized in one structure alone. On two occasions it involved the corpus callosum and the neighbouring hemispheral substance; in one instance it involved the head of the caudate nucleus and the lateral ventricle also. Two intraventricular angiomas, supplied by the choroidal arteries, involved the corpus striatum and the thalamus. Three cases of juxtapeduncular angiomas are described in this series. They were situated in the deep medial part of the temporal lobe, closely adhering to the peduncle, and supplied by branches of the posterior cerebral and the lateral choroidal arteries. In one case the malformation, which involved the thalamus, could be only partly removed. In six cases total extirpation was carried out. All patients ar alive and six are working. No symptoms which were not present before operation have appeared. The importance of adequate radiological studies prior to surgery is emphasized. Attention is drawn to the possibility of eventual obstruction in the CSF circulation in the postoperative period following intraventricular manipulation.


Talk it through.
Claire Westwood describes how she managed to improve communications between a child's parents and the nursing and medical teams.


The breakdown of spectrin produced by ultrasonication.
The application of carefully controlled ultrasonication to human erythrocyte membranes (ghosts) has been found to produce a selective breakdown of the two spectrin polypeptides. This breakdown increases with the time and the intensity of ultrasonication. The 240 000 molecular weight spectrin polypeptide is slightly more susceptible to ultrasonication than the 220 000 molecular weight polypeptide. Isolated spectrin behaves in an identical manner when ultrasonicated. When highly purified samples of spectrin are ultrasonicated the progressive reduction of the molecular weight of the products with increasing time is clearly apparent.


Return to Work in Cancer Patients: A Systematic Review and Meta-analysis.
Diseases and accidents bring about the disorder at someone's job insofar as one is not able to return to her/his previous work. These cases are related to the amount of occurred accidents, type of disease, and one's job. The aim of this study was to evaluate the factors that affect return to work (RTW) in cancer survivors using a systematic review and meta-analysis design. This is a systematic review and meta-analysis study. We searched the PubMed, Scopus, SID, Google, Elsevier, Google Scholar and Web of Science databases using following keywords: Return to work, cancer patients, employment status, cancer survivors from 2002 to 2017. The rate of return to work in cancer patients based on age group and risk factors was calculated using subgroup analysis. Data were analyzed using STATA software (version 11.1). The total sample size was 4675 people with a mean of 668 in each study. The frequency of studies in the world consists mainly of five studies (71.5%) from Europe continent (the Netherlands and Denmark) and two studies (28.5%) from Asia continent (Iran and Japan). The overall rate of RTW estimated at 72% (68%-77%). The percentage of RTW in Asia and Europe was 57% (50%-65%) and 52% (43%-60%), respectively. Surgery had the highest percentage of treatment options in patients with cancer with 46% (25%-68%), followed by radiotherapy and chemotherapy with 37% (29%-46%) and 36% (23%-49%), respectively. Breast cancer and gastrointestinal cancer were the most and less common type of cancers with 36% (19%-54%) and 16% (7%-26%), respectively. The overall rate of RTW estimated at 57%. Nonetheless, the faster diagnosis and regular screening could improve the survival rate of cancer patients and the increase of RTW.


N-nitrosoephedrine and N-nitrosopseudoephedrine: their dissolution, absorption, blood clearance and elimination studies.
Dissolution and absorption rates (in vitro); clearance from blood and elimination rates of N-nitrosoephedrine (NEP) and N-nitrosopseudophedrine (NPEP) in mice were determined. The two isomers obeyed first-order kinetics and from the slope of the regression line, the rate constant for each study was obtained. These constants were 0.023, 0.038 min-1 (dissolution); 0.192, 0.225 h-1 (stomach absorption); 2.898, 1.980 h-1 (intestinal absorption); 0.33, 0.55 h-1 (blood clearance) and 0.373, 0.393 h-1 (elimination from whole animal) of NEP and NPEP, respectively, and were tested by Student's t-test. Significant differences in the dissolution, absorption and blood clearance rates of NPEP from those of NEP have been observed (P less than 0.05-0.01). These differences are expected to exert their influence on the metabolic rates and the carcinogenic and/or spectral properties of NEP and NPEP, in a related pattern.


Behavioural, odontological and physical activity patterns of hypertense and control population.
Behavioural and multifactorial factors such as odontological and physical activity habits are controlling factors in hypertension. The aim of the present study was to analyze differences in behavioral, odontological and physical activity patterns of hypertense and control population. Fifty participants with hypertension (57.5±13.6 years) and 100 participants as control group with no hypertension disease (48.9±7.9 years) were interviewed via online questionnaire. Multifactorial items in oral behavioral, health habits and physical activity profile were analyzed by a compendium of questionnaires. Result showed how control group showed significantly lower age, weight, body mass index, TV hours per day, gastritis or heartburn, dental sensibility, and sick days last year, and significantly higher level of academic education, quality of sleep and daily toothbrushing than hypertension group. In conclusion our results showed that hypertense patients presented higher levels of overweight, poor sleep quality and sedentary behaviors than control participants. In addition, hypertense patients also presented poor odontological health, showing higher indices of gastritis, dental sensibility, and sick days per year. Both groups presented a low physical activity pattern. This information allows to better understand of a multifactorial disease, as well to the creation of protocols for intervention and prevention of this disease at the behavioral level and lifestyle.


Characterization of a new rat urinary metabolite of piperine by LC/NMR/MS studies.
Potential of piperine, an active alkaloid of black and long peppers, to increase the bioavailability of drugs in humans is of great clinical significance owing to its omnipresence in food. In an attempt to further study the reported differences in its metabolism in rats and humans, a new major urinary metabolite was detected in rat urine and plasma using HPLC. The metabolite was partially purified using reverse phase column chromatography on Sephadex((R))-LH 20 and characterized as 5-(3, 4-methylenedioxy phenyl)-2E,4E-pentadienoic acid-N-(3-yl propionic acid)-amide with the help of LC/NMR/positive ESI-MS studies. Complete mass fragmentation pattern could be assigned with MS/MS studies. The metabolite has a unique structure compared to the previously reported metabolites in that it retains methylenedioxy ring and conjugated double bonds while the piperidine ring is modified to form propionic acid group. Mechanism of formation of the metabolite by oxidation and cleavage of piperidine ring is proposed. Kidney appears to be the major excretion route for piperine metabolites in rats as no metabolite could be detected in feces.


Somatic mosaicism for copy-neutral loss of heterozygosity and DNA copy number variations in the human genome.
Somatic mosaicism denotes the presence of genetically distinct populations of somatic cells in one individual who has developed from a single fertilised oocyte. Mosaicism may result from a mutation that occurs during postzygotic development and is propagated to only a subset of the adult cells. Our aim was to investigate both somatic mosaicism for copy-neutral loss of heterozygosity (cn-LOH) events and DNA copy number variations (CNVs) in fully differentiated tissues. We studied panels of tissue samples (11-12 tissues per individual) from four autopsy subjects using high-resolution Illumina HumanOmniExpress-12 BeadChips to reveal the presence of possible intra-individual tissue-specific cn-LOH and CNV patterns. We detected five mosaic cn-LOH regions >5 Mb in some tissue samples in three out of four individuals. We also detected three CNVs that affected only a portion of the tissues studied in one out of four individuals. These three somatic CNVs range from 123 to 796 kb and are also found in the general population. An attempt was made to explain the succession of genomic events that led to the observed somatic genetic mosaicism under the assumption that the specific mosaic patterns of CNV and cn-LOH changes reflect their formation during the postzygotic embryonic development of germinal layers and organ systems. Our results give further support to the idea that somatic mosaicism for CNVs, and also cn-LOHs, is a common phenomenon in phenotypically normal humans. Thus, the examination of only a single tissue might not provide enough information to diagnose potentially deleterious CNVs within an individual. During routine CNV and cn-LOH analysis, DNA derived from a buccal swab can be used in addition to blood DNA to get information about the CNV/cn-LOH content in tissues of both mesodermal and ectodermal origin. Currently, the real frequency and possible phenotypic consequences of both CNVs and cn-LOHs that display somatic mosaicism remain largely unknown. To answer these questions, future studies should involve larger cohorts of individuals and a range of tissues.


Mechanism of PGE inhibition of catecholamine release from adrenal medulla.
Catecholamine (CA) secretion from the adrenal medulla was induced in vitro by acetylcholine (10(-4)M) (ACh), by incubation in potassium-free medium, by addition of ouabain (10(-3)M), by theophylline (10(-2)M) or by salbutamol (10(-6) and 6 x 10(-6) M). Theophylline and salbutamol, but not ACh, released CA in a calcium-free medium supplemented with 2mM EGTA. PGE2 significantly inhibited both CA secretion evoked by ACh and that evoked by salbutamol, i.e. both secretion dependent on, and independent of, extracellular calcium, PGE2 counteracted the increase of cAMP levels caused by ACh or salbutamol in adrenal medullary slices. PGE2 also diminished the salbutamol-induced activation of adenylate cyclase in an adrenal medullary membrane preparation, PGE2 reduced the rate of 45Ca efflux from slices of adrenal medulla preloaded with 45CaCl2. It is suggested that PGE2 inhibits CA secretion through the following sequence: inhibition of adenylate cyclase, a fall of cellular cAMP resulting in reduced release of calcium from intracellular binding sites and reduced free cytoplasmic calcium.


Targeting Accuracy of the Subthalamic Nucleus in Deep Brain Stimulation Surgery: Comparison Between 3 T T2-Weighted Magnetic Resonance Imaging and Microelectrode Recording Results.
Targeting accuracy in deep brain stimulation (DBS) surgery can be defined as the level of accordance between selected and anatomic real target reflected by characteristic electrophysiological results of microelectrode recording (MER). To determine the correspondence between the preoperative predicted target based on modern 3-T magnetic resonance imaging (MRI) and intraoperative MER results separately on the initial and consecutive second side of surgery. Retrospective cohort study of 86 trajectories of DBS electrodes implanted into the subthalamic nucleus (STN) of patients with Parkinson's disease. The entrance point of the electrode into the STN and the length of the electrode trajectory crossing the STN were determined by intraoperative MER findings and 3 T T2-weighted magnetic resonance images with 1-mm slice thickness. Average difference between MRI- and MER-based trajectory lengths crossing the STN was 0.28 ± 1.02 mm (95% CI: -0.51 to -0.05 mm). There was a statistically significant difference between the MRI- and MER-based entry points on the initial and second side of surgery (P = .04). Forty-three percent of the patients had a difference of more than ±1 mm of the MRI-based-predicted and the MER-based-determined entry points into the STN with values ranging from -3.0 to + 4.5 mm. STN MRI-based targeting is accurate in the majority of cases on the first and second side of surgery. In 43% of implanted electrodes, we found a relevant deviation of more than 1 mm, supporting the concept of MER as an important tool to guide and optimize targeting and electrode placement.


Improved reproducibility of simple quantitative indices from ⁹⁹mTc-GSA liver functional imaging.
We evaluated intra- and interoperator reproducibilities in calculating the conventional indices HH15 and LHL15 from (99m)Tc-diethylenetriamine pentaacetic acid galactosyl human serum albumin ((99m)Tc-GSA) scintigraphy, and proposed new, simple methods for the calculation of quantitative indices. The results of (99m)Tc-GSA scintigraphy in 33 patients were retrospectively analyzed. Heart and liver ROIs were drawn manually to cover cardiac blood pool and entire liver, respectively, and HH15 and LHL15 were calculated. In addition, square regions of interest (ROIs) of fixed sizes were placed at the highest activity in blood pool and the liver. Using the square heart ROI, sHH15, an equivalent of HH15, was computed. Fractional liver uptake at 15 min (FLU15) was calculated using the square heart and liver ROIs. Intra- and interoperator reproducibilities, as well as correlation with Indocyanine green retention rate at 15 min (ICG R15), were assessed for these four indices by linear regression analysis. Substantial intra- and interoperator variabilities were found for HH15 and LHL15. The correlation coefficients for intra- and interoperator comparisons were 0.884 and 0.869 for HH15, respectively, and 0.919 and 0.917 for LHL15, respectively. The use of square ROIs instead of hand-drawn ROIs improved reproducibility. The correlation coefficients for intra- and interoperator comparisons were 0.988 and 0.973 for sHH15, respectively, and 0.989 and 0.975 for FLU15, respectively. Correlation with ICG R15 was better for sHH15 (r = 0.619) and FLU15 (r = -0.656) than for HH15 (r = 0.439) and LHL15 (r = -0.490). HH15 and LHL15 showed substantial intra- and interoperator variabilities, and the use of square ROIs are indicated to provide better reproducibility.


Stem cell-derived β cells go in monkeys.
Du et al. transplanted β cells derived from pluripotent stem cells in diabetic monkeys for the first time, as an intermediate stage toward clinical translation. They observed benefits unfolding over months but also observed immune rejection of the grafts by 5-6 months.


Late-onset facioscapulohumeral muscular dystrophy type 1 in previously undiagnosed families: Presenting clinical features in an often-misdiagnosed disorder.
In our experience, patients with late-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1) are frequently misdiagnosed, some for many years. The aim of this report is to document this clinical experience including the presenting symptoms and misdiagnoses and to discuss the challenges in diagnosing patients with late-onset FSHD1. We performed a retrospective medical record review and recorded clinical data on patients with a genetically confirmed diagnosis of FSHD1, who began to have symptoms at 50 years of age or older, and either had no family history of FSHD1 or had a history of an undiagnosed weakness in a family member. Thirteen patients, 7 men and 6 women, met the study inclusion criteria. Age of onset ranged from 52 to 74 (mean, 59.8) years, age of diagnosis ranged from 54 to 80 (mean, 66.5) years, and duration of symptoms from onset to diagnosis was 1 to 15 (mean, 6.7) years. Prior diagnoses included lumbosacral polyradiculopathy in five (38%); statin-related myopathy in two (15%); and one each of polymyositis, inclusion-body myositis, distal myopathy, limb-girdle muscular dystrophy, unspecific myopathy, and unspecified scapular winging. For eight patients (62%), family history was suspected in deceased members or if by confirmed DNA test postdiagnosis. The diagnosis of late-onset FSHD1 is often delayed by many years with patients frequently receiving misdiagnoses. FSHD1 may not be considered in the differential diagnosis of late-onset weakness due to its rarity and because its clinical features are subtler, nonspecific, and mimic other neuromuscular disorders.


Transient and sustained BOLD responses to sustained visual stimulation.
Examining the transients of the blood-oxygenation-level-dependent (BOLD) signal using functional magnetic resonance imaging is a tool to probe basic brain physiology. In addition to the so-called initial dip and poststimulus undershoot of the BOLD signal, occasionally, overshoot at the beginning and at the end of stimulation and stimulus onset and offset ('phasic') responses are observed. Hemifield visual stimulation was used in human subjects to study the latter transients. As expected, sustained ('tonic') stimulus-correlated contralateral activation in the visual cortex and LGN was observed. Interestingly, bilateral phasic responses were observed, which only partly overlapped with the tonic network and which would have been missed using a standard analysis. A biomechanical model of the BOLD signal ('balloon model') indicated that, in addition to phasic neuronal activity, vascular uncoupling can also give rise to phasic BOLD signals. Thus, additional physiological information (i.e., cerebral blood flow) and examination of spatial distribution of the activity might help to assess the BOLD signal transients correctly. In the current study, although vascular uncoupled responses cannot be ruled out as an explanation of the observed phasic BOLD network, the spatial distribution argues that sustained hemifield visual stimulation evokes both bilateral phasic and contralateral sustained neuronal responses. As a consequence, in rapid event-related experimental designs, both the phasic and tonic networks cannot be separated, possibly confounding the interpretation of BOLD signal data. Furthermore, a combination of phasic and tonic responses in the same region of interest might also mimic a BOLD response typically observed in adaptation experiments.